Proteinopathy

Last updated
Proteinopathy
Proteopathy Abeta deposits in Alzheimer disease.jpg
Micrograph of a section of the cerebral cortex from a person with Alzheimer's disease, immunostained with an antibody to amyloid beta (brown), a protein fragment that accumulates in amyloid plaques and cerebral amyloid angiopathy. 10X microscope objective.

In medicine, proteinopathy ([pref. protein]; -pathy [suff. disease]; proteinopathiespl.; proteinopathicadj), or proteopathy, protein conformational disorder, or protein misfolding disease, is a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the function of cells, tissues and organs of the body. [1] [2]

Contents

Often the proteins fail to fold into their normal configuration; in this misfolded state, the proteins can become toxic in some way (a toxic gain-of-function) or they can lose their normal function. [3] The proteinopathies include such diseases as Creutzfeldt–Jakob disease (and a variant associated with mad cow disease) and other prion diseases, Alzheimer's disease, Parkinson's disease, amyloidosis, multiple system atrophy, and a wide range of other disorders. [2] [4] [5] [6] [7] [8] The term proteopathy was first proposed in 2000 by Lary Walker and Harry LeVine. [1]

The concept of proteopathy can trace its origins to the mid-19th century, when, in 1854, Rudolf Virchow coined the term amyloid ("starch-like") to describe a substance in cerebral corpora amylacea that exhibited a chemical reaction resembling that of cellulose. In 1859, Friedreich and Kekulé demonstrated that, rather than consisting of cellulose, "amyloid" actually is rich in protein. [9] Subsequent research has shown that many different proteins can form amyloid, and that all amyloids show birefringence in cross-polarized light after staining with the dye Congo red, as well as a fibrillar ultrastructure when viewed with an electron microscope. [9] However, some proteinaceous lesions lack birefringence and contain few or no classical amyloid fibrils, such as the diffuse deposits of amyloid beta (Aβ) protein in the brains of people with Alzheimer's. [10] Furthermore, evidence has emerged that small, non-fibrillar protein aggregates known as oligomers are toxic to the cells of an affected organ, and that amyloidogenic proteins in their fibrillar form may be relatively benign. [11] [12]

Micrograph of amyloid in a section of liver that has been stained with the dye Congo red and viewed with crossed polarizing filters, yielding a typical orange-greenish birefringence. 20X microscope objective; the scale bar is 100 microns (0.1mm). Amyloid Liver Congo Red Bar=100um.jpg
Micrograph of amyloid in a section of liver that has been stained with the dye Congo red and viewed with crossed polarizing filters, yielding a typical orange-greenish birefringence. 20X microscope objective; the scale bar is 100 microns (0.1mm).

Pathophysiology

In most, if not all proteinopathies, a change in the 3-dimensional folding conformation increases the tendency of a specific protein to bind to itself. [5] In this aggregated form, the protein is resistant to clearance and can interfere with the normal capacity of the affected organs. In some cases, misfolding of the protein results in a loss of its usual function. For example, cystic fibrosis is caused by a defective cystic fibrosis transmembrane conductance regulator (CFTR) protein, [3] and in amyotrophic lateral sclerosis / frontotemporal lobar degeneration (FTLD), certain gene-regulating proteins inappropriately aggregate in the cytoplasm, and thus are unable to perform their normal tasks within the nucleus. [13] [14]

Because proteins share a common structural feature known as the polypeptide backbone, all proteins have the potential to misfold under some circumstances. [15] However, only a relatively small number of proteins are linked to proteopathic disorders, possibly due to structural idiosyncrasies of the vulnerable proteins. For example, proteins that are normally unfolded or relatively unstable as monomers (that is, as single, unbound protein molecules) are more likely to misfold into an abnormal conformation. [5] [15] [16] In nearly all instances, the disease-causing molecular configuration involves an increase in beta-sheet secondary structure of the protein. [5] [15] [17] [18] [19]

The abnormal proteins in some proteopathies have been shown to fold into multiple 3-dimensional shapes; these variant, proteinaceous structures are defined by their different pathogenic, biochemical, and conformational properties. [20] They have been most thoroughly studied with regard to prion disease, and are referred to as protein strains. [21] [22]

Micrograph of immunostained a-synuclein (brown) in Lewy bodies (large clumps) and Lewy neurites (thread-like structures) in the cerebral cortex of a patient with Lewy body disease, a synucleinopathy. 40X microscope objective. Immunostaining (brown) of alpha-synuclein in Lewy Bodies and Lewy Neurites in the neocortex of a patient with Lewy Body Disease.jpg
Micrograph of immunostained α-synuclein (brown) in Lewy bodies (large clumps) and Lewy neurites (thread-like structures) in the cerebral cortex of a patient with Lewy body disease, a synucleinopathy. 40X microscope objective.

The likelihood that proteinopathy will develop is increased by certain risk factors that promote the self-assembly of a protein. These include destabilizing changes in the primary amino acid sequence of the protein, post-translational modifications (such as hyperphosphorylation), changes in temperature or pH, an increase in production of a protein, or a decrease in its clearance. [1] [5] [15] Advancing age is a strong risk factor, [1] as is traumatic brain injury. [23] [24] In the aging brain, multiple proteopathies can overlap. [25] For example, in addition to tauopathy and Aβ-amyloidosis (which coexist as key pathologic features of Alzheimer's disease), many Alzheimer patients have concomitant synucleinopathy (Lewy bodies) in the brain. [26]

It is hypothesized that chaperones and co-chaperones (proteins that assist protein folding) may antagonize proteotoxicity during aging and in protein misfolding-diseases to maintain proteostasis. [27] [28] [29]

Seeded induction

Some proteins can be induced to form abnormal assemblies by exposure to the same (or similar) protein that has folded into a disease-causing conformation, a process called 'seeding' or 'permissive templating'. [30] [31] In this way, the disease state can be brought about in a susceptible host by the introduction of diseased tissue extract from an affected donor. The best known forms of inducible proteopathy are prion diseases, [32] which can be transmitted by exposure of a host organism to purified prion protein in a disease-causing conformation. [33] [34]

There is now evidence that other proteinopathies can be induced by a similar mechanism, including Aβ amyloidosis, amyloid A (AA) amyloidosis, and apolipoprotein AII amyloidosis, [31] [35] tauopathy, [36] synucleinopathy, [37] [38] [39] [40] and the aggregation of superoxide dismutase-1 (SOD1), [41] [42] polyglutamine, [43] [44] and TAR DNA-binding protein-43 (TDP-43). [45]

In all of these instances, an aberrant form of the protein itself appears to be the pathogenic agent. In some cases, the deposition of one type of protein can be experimentally induced by aggregated assemblies of other proteins that are rich in β-sheet structure, possibly because of structural complementarity of the protein molecules. For example, AA amyloidosis can be stimulated in mice by such diverse macromolecules as silk, the yeast amyloid Sup35, and curli fibrils from the bacterium Escherichia coli . [46] AII amyloid can be induced in mice by a variety of β-sheet rich amyloid fibrils, [47] and cerebral tauopathy can be induced by brain extracts that are rich in aggregated Aβ. [48] There is also experimental evidence for cross-seeding between prion protein and Aβ. [49] In general, such heterologous seeding is less efficient than is seeding by a corrupted form of the same protein.

List of proteinopathies

ProteinopathyMajor aggregating protein
Alzheimer's disease [16] Amyloid β peptide (Aβ); Tau protein (see tauopathies)
Cerebral β-amyloid angiopathy [50] Amyloid β peptide (Aβ)
Retinal ganglion cell degeneration in glaucoma [51] Amyloid β peptide (Aβ)
Prion diseases (multiple) [52] Prion protein
Parkinson's disease and other synucleinopathies (multiple) [53] α-Synuclein
Tauopathies (multiple) [54] Microtubule-associated protein tau (Tau protein)
Frontotemporal lobar degeneration (FTLD) (Ubi+, Tau-) [55] TDP-43
FTLD–FUS [55] Fused in sarcoma (FUS) protein
Amyotrophic lateral sclerosis (ALS) [56] [57] Superoxide dismutase, TDP-43, FUS, C9ORF72, ubiquilin-2 (UBQLN2)
Huntington's disease and other trinucleotide repeat disorders (multiple) [58] [59] Proteins with tandem glutamine expansions
Familial British dementia [50] ABri
Familial Danish dementia [50] ADan
Hereditary cerebral hemorrhage with amyloidosis (Icelandic) (HCHWA-I) [50] Cystatin C
CADASIL [60] Notch3
Alexander disease [61] Glial fibrillary acidic protein (GFAP)
Pelizaeus-Merzbacher disease proteolipid protein (PLP)
Seipinopathies [62] Seipin
Familial amyloidotic neuropathy, Senile systemic amyloidosis Transthyretin [63]
Serpinopathies (multiple) [64] Serpins
AL (light chain) amyloidosis (primary systemic amyloidosis)Monoclonal immunoglobulin light chains [63]
AH (heavy chain) amyloidosis Immunoglobulin heavy chains [63]
AA (secondary) amyloidosis Amyloid A protein [63]
Type II diabetes [65] Islet amyloid polypeptide (IAPP; amylin)
Aortic medial amyloidosis Medin (lactadherin) [63]
ApoAI amyloidosis Apolipoprotein AI [63]
ApoAII amyloidosis Apolipoprotein AII [63]
ApoAIV amyloidosis Apolipoprotein AIV [63]
Familial amyloidosis of the Finnish type (FAF) Gelsolin [63]
Lysozyme amyloidosis Lysozyme [63]
Fibrinogen amyloidosis Fibrinogen [63]
Dialysis amyloidosis Beta-2 microglobulin [63]
Inclusion body myositis/myopathy [66] Amyloid β peptide (Aβ)
Cataracts [67] Crystallins
Retinitis pigmentosa with rhodopsin mutations [68] rhodopsin
Medullary thyroid carcinoma Calcitonin [63]
Cardiac atrial amyloidosis Atrial natriuretic factor [63]
Pituitary prolactinoma Prolactin [63]
Hereditary lattice corneal dystrophy Keratoepithelin [63]
Cutaneous lichen amyloidosis [69] Keratins
Mallory bodies [70] Keratin intermediate filament proteins
Corneal lactoferrin amyloidosis Lactoferrin [63]
Pulmonary alveolar proteinosis Surfactant protein C (SP-C) [63]
Odontogenic (Pindborg) tumor amyloid Odontogenic ameloblast-associated protein [63]
Seminal vesicle amyloid Semenogelin I [63]
Apolipoprotein C2 amyloidosis Apolipoprotein C2 (ApoC2) [63]
Apolipoprotein C3 amyloidosis Apolipoprotein C3 (ApoC3) [63]
Lect2 amyloidosis Leukocyte chemotactic factor-2 (Lect2) [63]
Insulin amyloidosis Insulin [63]
Galectin-7 amyloidosis (primary localized cutaneous amyloidosis) Galectin-7 (Gal7) [63]
Corneodesmosin amyloidosis Corneodesmosin [63]
Enfuvirtide amyloidosis [71] Enfuvirtide [63]
Cystic fibrosis [72] cystic fibrosis transmembrane conductance regulator (CFTR) protein
Sickle cell disease [73] Hemoglobin
Plasma cell dyscrasias (monoclonal gammopathies) gamma globulin
Exfoliation syndrome [74] aka pseudoexfoliation syndrome aggregated fibrillar material esp. LOXL1

Management

The development of effective treatments for many proteopathies has been challenging. [75] [76] Because the proteopathies often involve different proteins arising from different sources, treatment strategies must be customized to each disorder; however, general therapeutic approaches include maintaining the function of affected organs, reducing the formation of the disease-causing proteins, preventing the proteins from misfolding and/or aggregating, or promoting their removal. [77] [75] [78] For example, in Alzheimer's disease, researchers are seeking ways to reduce the production of the disease-associated protein Aβ by inhibiting the enzymes that free it from its parent protein. [76] Another strategy is to use antibodies to neutralize specific proteins by active or passive immunization. [79] In some proteopathies, inhibiting the toxic effects of protein oligomers might be beneficial. [80]

For example, Amyloid A (AA) amyloidosis can be reduced by treating the inflammatory state that increases the amount of the protein in the blood (referred to as serum amyloid A, or SAA). [75] In immunoglobulin light chain amyloidosis (AL amyloidosis), chemotherapy can be used to lower the number of the blood cells that make the light chain protein that forms amyloid in various bodily organs. [81] Transthyretin (TTR) amyloidosis (ATTR) results from the deposition of misfolded TTR in multiple organs. [82] Because TTR is mainly produced in the liver, TTR amyloidosis can be slowed in some hereditary cases by liver transplantation. [83] TTR amyloidosis also can be treated by stabilizing the normal assemblies of the protein (called tetramers because they consist of four TTR molecules bound together). Stabilization prevents individual TTR molecules from escaping, misfolding, and aggregating into amyloid. [84] [85]

Several other treatment strategies for proteopathies are being investigated, including small molecules and biologic medicines such as small interfering RNAs, antisense oligonucleotides, peptides, and engineered immune cells. [84] [81] [86] [87] In some cases, multiple therapeutic agents may be combined to improve effectiveness. [81] [88]

Additional images

See also

Related Research Articles

<span class="mw-page-title-main">Prion</span> Pathogenic type of misfolded protein

A prion is a misfolded protein that induces misfolding in normal variants of the same protein, leading to cellular death. Prions are responsible for prion diseases, known as transmissible spongiform encephalopathy (TSEs), which are fatal and transmissible neurodegenerative diseases affecting both humans and animals. These proteins can misfold sporadically, due to genetic mutations, or by exposure to an already misfolded protein, leading to an abnormal three-dimensional structure that can propagate misfolding in other proteins.

<span class="mw-page-title-main">Amyloid</span> Insoluble protein aggregate with a fibrillar morphology

Amyloids are aggregates of proteins characterised by a fibrillar morphology of typically 7–13 nm in diameter, a β-sheet secondary structure and ability to be stained by particular dyes, such as Congo red. In the human body, amyloids have been linked to the development of various diseases. Pathogenic amyloids form when previously healthy proteins lose their normal structure and physiological functions (misfolding) and form fibrous deposits within and around cells. These protein misfolding and deposition processes disrupt the healthy function of tissues and organs.

<span class="mw-page-title-main">Alpha-synuclein</span> Protein found in humans

Alpha-synuclein (aSyn) is a protein that, in humans, is encoded by the SNCA gene. Alpha-synuclein is a neuronal protein that regulates synaptic vesicle trafficking and subsequent neurotransmitter release.

<span class="mw-page-title-main">Amyloidosis</span> Metabolic disease involving abnormal deposited amyloid proteins

Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weight loss, shortness of breath, palpitations, and feeling faint with standing. In AL amyloidosis, specific indicators can include enlargement of the tongue and periorbital purpura. In wild-type ATTR amyloidosis, non-cardiac symptoms include: bilateral carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, small fiber neuropathy, and autonomic dysfunction.

<span class="mw-page-title-main">Transthyretin</span> Serum protein related to amyloid diseases

Transthyretin (TTR or TBPA) is a transport protein in the plasma and cerebrospinal fluid that transports the thyroid hormone thyroxine (T4) and retinol to the liver. This is how transthyretin gained its name: transports thyroxine and retinol. The liver secretes TTR into the blood, and the choroid plexus secretes TTR into the cerebrospinal fluid.

<span class="mw-page-title-main">Tau protein</span> Group of six protein isoforms produced from the MAPT gene

The tau proteins form a group of six highly soluble protein isoforms produced by alternative splicing from the gene MAPT. They have roles primarily in maintaining the stability of microtubules in axons and are abundant in the neurons of the central nervous system (CNS), where the cerebral cortex has the highest abundance. They are less common elsewhere but are also expressed at very low levels in CNS astrocytes and oligodendrocytes.

<span class="mw-page-title-main">Amyloid beta</span> Group of peptides

Amyloid beta denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate presentation. Both neurons and oligodendrocytes produce and release Aβ in the brain, contributing to formation of amyloid plaques. Aβ molecules can aggregate to form flexible soluble oligomers which may exist in several forms. It is now believed that certain misfolded oligomers can induce other Aβ molecules to also take the misfolded oligomeric form, leading to a chain reaction akin to a prion infection. The oligomers are toxic to nerve cells. The other protein implicated in Alzheimer's disease, tau protein, also forms such prion-like misfolded oligomers, and there is some evidence that misfolded Aβ can induce tau to misfold.

<span class="mw-page-title-main">Amyloid plaques</span> Extracellular deposits of the amyloid beta protein

Amyloid plaques are extracellular deposits of amyloid beta (Aβ) protein that present mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of microglia and astrocytes can be associated with amyloid plaques. Some plaques occur in the brain as a result of aging, but large numbers of plaques and neurofibrillary tangles are characteristic features of Alzheimer's disease. The plaques are highly variable in shape and size; in tissue sections immunostained for Aβ, they comprise a log-normal size distribution curve, with an average plaque area of 400-450 square micrometers (μm2). The smallest plaques, which often consist of diffuse deposits of Aβ, are particularly numerous. Plaques form when Aβ misfolds and aggregates into oligomers and longer polymers, the latter of which are characteristic of amyloid.

<span class="mw-page-title-main">Major prion protein</span> Protein involved in multiple prion diseases

The major prion protein (PrP) is encoded in the human body by the PRNP gene also known as CD230. Expression of the protein is most predominant in the nervous system but occurs in many other tissues throughout the body.

<span class="mw-page-title-main">Tauopathy</span> Medical condition

Tauopathies are a class of neurodegenerative diseases characterized by the aggregation of abnormal tau protein. Hyperphosphorylation of tau proteins causes them to dissociate from microtubules and form insoluble aggregates called neurofibrillary tangles. Various neuropathologic phenotypes have been described based on the anatomical regions and cell types involved as well as the unique tau isoforms making up these deposits. The designation 'primary tauopathy' is assigned to disorders where the predominant feature is the deposition of tau protein. Alternatively, diseases exhibiting tau pathologies attributed to different and varied underlying causes are termed 'secondary tauopathies'. Some neuropathologic phenotypes involving tau protein are Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy, and corticobasal degeneration.

<span class="mw-page-title-main">Neurodegenerative disease</span> Central nervous system disease

A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, tauopathies, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.

Karen K. Hsiao Ashe is a professor at the Department of Neurology and Neuroscience at the University of Minnesota (UMN) Medical School, where she holds the Edmund Wallace and Anne Marie Tulloch Chairs in Neurology and Neuroscience. She is the founding director of the N. Bud Grossman Center for Memory Research and Care, and her specific research interest is memory loss resulting from Alzheimer's disease and related dementias. Her research has included the development of an animal model of Alzheimer's.

The biochemistry of Alzheimer's disease, the most common cause of dementia, is not yet very well understood. Alzheimer's disease (AD) has been identified as a proteopathy: a protein misfolding disease due to the accumulation of abnormally folded amyloid beta (Aβ) protein in the brain. Amyloid beta is a short peptide that is an abnormal proteolytic byproduct of the transmembrane protein amyloid-beta precursor protein (APP), whose function is unclear but thought to be involved in neuronal development. The presenilins are components of proteolytic complex involved in APP processing and degradation.

<span class="mw-page-title-main">Cardiac amyloidosis</span> Medical condition

Cardiac amyloidosis is a subcategory of amyloidosis where there is depositing of the protein amyloid in the cardiac muscle and surrounding tissues. Amyloid, a misfolded and insoluble protein, can become a deposit in the heart's atria, valves, or ventricles. These deposits can cause thickening of different sections of the heart, leading to decreased cardiac function. The overall decrease in cardiac function leads to a plethora of symptoms. This multisystem disease was often misdiagnosed, with a corrected analysis only during autopsy. Advancements of technologies have increased earlier accuracy of diagnosis. Cardiac amyloidosis has multiple sub-types including light chain, familial, and senile. One of the most studied types is light chain cardiac amyloidosis. Prognosis depends on the extent of the deposits in the body and the type of amyloidosis. New treatment methods are actively being researched in regards to the treatment of heart failure and specific cardiac amyloidosis problems.

The familial amyloid neuropathies are a rare group of autosomal dominant diseases wherein the autonomic nervous system and/or other nerves are compromised by protein aggregation and/or amyloid fibril formation.

The ion channel hypothesis of Alzheimer's disease (AD), also known as the channel hypothesis or the amyloid beta ion channel hypothesis, is a more recent variant of the amyloid hypothesis of AD, which identifies amyloid beta (Aβ) as the underlying cause of neurotoxicity seen in AD. While the traditional formulation of the amyloid hypothesis pinpoints insoluble, fibrillar aggregates of Aβ as the basis of disruption of calcium ion homeostasis and subsequent apoptosis in AD, the ion channel hypothesis in 1993 introduced the possibility of an ion-channel-forming oligomer of soluble, non-fibrillar Aβ as the cytotoxic species allowing unregulated calcium influx into neurons in AD.

Mathias Jucker is a Swiss neuroscientist, Professor, and a Director at the Hertie Institute for Clinical Brain Research of the University of Tübingen. He is also a group leader at the German Center for Neurodegenerative Diseases in Tübingen. Jucker is known for his research on the basic biologic mechanisms underlying brain aging and Alzheimer's disease.

Lary Walker is an American neuroscientist and researcher at Emory University in Atlanta, Georgia. He is Associate Director of the Goizueta Alzheimer's Disease Research Center at Emory, and he is known for his research on the role of abnormal proteins in the causation of Alzheimer's disease.

Hilal Lashuel is an American-Yemeni neuroscientist and chemist, currently an associate professor at the EPFL. His research focuses on protein misfolding and aggregation in the pathogenesis of Alzheimer's and Parkinson's diseases.

Li Gan is a neuroscientist and professor at Weill Cornell Medical College. She is known for her discovery of pathogenic tau protein acetylation in tauopathies and mechanisms of microglia dysfunction in neurodegeneration.

References

  1. 1 2 3 4 Walker LC, LeVine H (2000). "The cerebral proteopathies". Neurobiology of Aging. 21 (4): 559–61. doi:10.1016/S0197-4580(00)00160-3. PMID   10924770. S2CID   54314137.
  2. 1 2 Walker LC, LeVine H (2000). "The cerebral proteopathies: neurodegenerative disorders of protein conformation and assembly". Molecular Neurobiology. 21 (1–2): 83–95. doi:10.1385/MN:21:1-2:083. PMID   11327151. S2CID   32618330.
  3. 1 2 Luheshi LM, Crowther DC, Dobson CM (February 2008). "Protein misfolding and disease: from the test tube to the organism". Current Opinion in Chemical Biology. 12 (1): 25–31. doi:10.1016/j.cbpa.2008.02.011. PMID   18295611.
  4. ↑ Chiti F, Dobson CM (2006). "Protein misfolding, functional amyloid, and human disease". Annual Review of Biochemistry. 75 (1): 333–66. doi:10.1146/annurev.biochem.75.101304.123901. PMID   16756495. S2CID   23797549.
  5. 1 2 3 4 5 Carrell RW, Lomas DA (July 1997). "Conformational disease". Lancet. 350 (9071): 134–8. doi:10.1016/S0140-6736(97)02073-4. PMID   9228977. S2CID   39124185.
  6. ↑ Westermark P, Benson MD, Buxbaum JN, Cohen AS, Frangione B, Ikeda S, Masters CL, Merlini G, Saraiva MJ, Sipe JD (September 2007). "A primer of amyloid nomenclature". Amyloid. 14 (3): 179–83. doi:10.1080/13506120701460923. PMID   17701465. S2CID   12480248.
  7. ↑ Westermark GT, Fändrich M, Lundmark K, Westermark P (January 2018). "Noncerebral Amyloidoses: Aspects on Seeding, Cross-Seeding, and Transmission". Cold Spring Harbor Perspectives in Medicine. 8 (1): a024323. doi: 10.1101/cshperspect.a024323 . PMC   5749146 . PMID   28108533.
  8. ↑ Prusiner SB (2013). "Biology and genetics of prions causing neurodegeneration". Annual Review of Genetics. 47: 601–23. doi:10.1146/annurev-genet-110711-155524. PMC   4010318 . PMID   24274755.
  9. 1 2 Sipe JD, Cohen AS (June 2000). "Review: history of the amyloid fibril". Journal of Structural Biology. 130 (2–3): 88–98. doi:10.1006/jsbi.2000.4221. PMID   10940217.
  10. ↑ Wisniewski HM, Sadowski M, Jakubowska-Sadowska K, Tarnawski M, Wegiel J (July 1998). "Diffuse, lake-like amyloid-beta deposits in the parvopyramidal layer of the presubiculum in Alzheimer disease". Journal of Neuropathology and Experimental Neurology. 57 (7): 674–83. doi: 10.1097/00005072-199807000-00004 . PMID   9690671.
  11. ↑ Glabe CG (April 2006). "Common mechanisms of amyloid oligomer pathogenesis in degenerative disease". Neurobiology of Aging. 27 (4): 570–5. doi:10.1016/j.neurobiolaging.2005.04.017. PMID   16481071. S2CID   32899741.
  12. ↑ Gadad BS, Britton GB, Rao KS (2011). "Targeting oligomers in neurodegenerative disorders: lessons from α-synuclein, tau, and amyloid-β peptide". Journal of Alzheimer's Disease. 24 (Suppl 2): 223–32. doi:10.3233/JAD-2011-110182. PMID   21460436.
  13. ↑ Ito D, Suzuki N (October 2011). "Conjoint pathologic cascades mediated by ALS/FTLD-U linked RNA-binding proteins TDP-43 and FUS". Neurology. 77 (17): 1636–43. doi:10.1212/WNL.0b013e3182343365. PMC   3198978 . PMID   21956718.
  14. ↑ Wolozin B, Apicco D (2015). "RNA Binding Proteins and the Genesis of Neurodegenerative Diseases". GeNeDis 2014. Advances in Experimental Medicine and Biology. Vol. 822. pp. 11–5. doi:10.1007/978-3-319-08927-0_3. ISBN   978-3-319-08926-3. PMC   4694570 . PMID   25416971.
  15. 1 2 3 4 Dobson CM (September 1999). "Protein misfolding, evolution and disease". Trends in Biochemical Sciences. 24 (9): 329–32. doi:10.1016/S0968-0004(99)01445-0. PMID   10470028.
  16. 1 2 Jucker M, Walker LC (September 2013). "Self-propagation of pathogenic protein aggregates in neurodegenerative diseases". Nature. 501 (7465): 45–51. Bibcode:2013Natur.501...45J. doi:10.1038/nature12481. PMC   3963807 . PMID   24005412.
  17. ↑ Selkoe DJ (December 2003). "Folding proteins in fatal ways". Nature. 426 (6968): 900–4. Bibcode:2003Natur.426..900S. doi:10.1038/nature02264. PMID   14685251. S2CID   6451881.
  18. ↑ Eisenberg D, Jucker M (March 2012). "The amyloid state of proteins in human diseases". Cell. 148 (6): 1188–203. doi:10.1016/j.cell.2012.02.022. PMC   3353745 . PMID   22424229.
  19. ↑ Röhr D, Boon BD (December 2020). "Label-free vibrational imaging of different Aβ plaque types in Alzheimer's disease reveals sequential events in plaque development". Acta Neuropathologica Communications. 8 (1): 222. doi: 10.1186/s40478-020-01091-5 . PMC   7733282 . PMID   33308303.
  20. ↑ Walker LC (November 2016). "Proteopathic Strains and the Heterogeneity of Neurodegenerative Diseases". Annual Review of Genetics. 50: 329–346. doi:10.1146/annurev-genet-120215-034943. PMC   6690197 . PMID   27893962.
  21. ↑ Collinge J, Clarke AR (November 2007). "A general model of prion strains and their pathogenicity". Science. 318 (5852): 930–6. Bibcode:2007Sci...318..930C. doi:10.1126/science.1138718. PMID   17991853. S2CID   8993435.
  22. ↑ Colby DW, Prusiner SB (September 2011). "De novo generation of prion strains". Nature Reviews. Microbiology. 9 (11): 771–7. doi:10.1038/nrmicro2650. PMC   3924856 . PMID   21947062.
  23. ↑ DeKosky ST, Ikonomovic MD, Gandy S (September 2010). "Traumatic brain injury--football, warfare, and long-term effects". The New England Journal of Medicine. 363 (14): 1293–6. doi:10.1056/NEJMp1007051. PMID   20879875.
  24. ↑ McKee AC, Stein TD, Kiernan PT, Alvarez VE (May 2015). "The neuropathology of chronic traumatic encephalopathy". Brain Pathology. 25 (3): 350–64. doi:10.1111/bpa.12248. PMC   4526170 . PMID   25904048.
  25. ↑ Nelson PT, Alafuzoff I, Bigio EH, Bouras C, Braak H, Cairns NJ, Castellani RJ, Crain BJ, Davies P, Del Tredici K, Duyckaerts C, Frosch MP, Haroutunian V, Hof PR, Hulette CM, Hyman BT, Iwatsubo T, Jellinger KA, Jicha GA, Kövari E, Kukull WA, Leverenz JB, Love S, Mackenzie IR, Mann DM, Masliah E, McKee AC, Montine TJ, Morris JC, Schneider JA, Sonnen JA, Thal DR, Trojanowski JQ, Troncoso JC, Wisniewski T, Woltjer RL, Beach TG (May 2012). "Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature". Journal of Neuropathology and Experimental Neurology. 71 (5): 362–81. doi:10.1097/NEN.0b013e31825018f7. PMC   3560290 . PMID   22487856.
  26. ↑ Mrak RE, Griffin WS (2007). "Dementia with Lewy bodies: Definition, diagnosis, and pathogenic relationship to Alzheimer's disease". Neuropsychiatric Disease and Treatment. 3 (5): 619–25. PMC   2656298 . PMID   19300591.
  27. ↑ Douglas PM, Summers DW, Cyr DM (2009). "Molecular chaperones antagonize proteotoxicity by differentially modulating protein aggregation pathways". Prion. 3 (2): 51–8. doi:10.4161/pri.3.2.8587. PMC   2712599 . PMID   19421006.
  28. ↑ Brehme M, Voisine C, Rolland T, Wachi S, Soper JH, Zhu Y, Orton K, Villella A, Garza D, Vidal M, Ge H, Morimoto RI (November 2014). "A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease". Cell Reports. 9 (3): 1135–50. doi:10.1016/j.celrep.2014.09.042. PMC   4255334 . PMID   25437566.
  29. ↑ Brehme M, Voisine C (August 2016). "Model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicity". Disease Models & Mechanisms. 9 (8): 823–38. doi:10.1242/dmm.024703. PMC   5007983 . PMID   27491084.
  30. ↑ Hardy J (August 2005). "Expression of normal sequence pathogenic proteins for neurodegenerative disease contributes to disease risk: 'permissive templating' as a general mechanism underlying neurodegeneration". Biochemical Society Transactions. 33 (Pt 4): 578–81. doi:10.1042/BST0330578. PMID   16042548.
  31. 1 2 Walker LC, Levine H, Mattson MP, Jucker M (August 2006). "Inducible proteopathies". Trends in Neurosciences. 29 (8): 438–43. doi:10.1016/j.tins.2006.06.010. PMC   10725716 . PMID   16806508. S2CID   46630402.
  32. ↑ Prusiner SB (May 2001). "Shattuck lecture--neurodegenerative diseases and prions". The New England Journal of Medicine. 344 (20): 1516–26. doi: 10.1056/NEJM200105173442006 . PMID   11357156.
  33. ↑ Zou WQ, Gambetti P (April 2005). "From microbes to prions the final proof of the prion hypothesis". Cell. 121 (2): 155–7. doi: 10.1016/j.cell.2005.04.002 . PMID   15851020.
  34. ↑ Ma J (2012). "The role of cofactors in prion propagation and infectivity". PLOS Pathogens. 8 (4): e1002589. doi: 10.1371/journal.ppat.1002589 . PMC   3325206 . PMID   22511864.
  35. ↑ Meyer-Luehmann M, Coomaraswamy J, Bolmont T, Kaeser S, Schaefer C, Kilger E, Neuenschwander A, Abramowski D, Frey P, Jaton AL, Vigouret JM, Paganetti P, Walsh DM, Mathews PM, Ghiso J, Staufenbiel M, Walker LC, Jucker M (September 2006). "Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host". Science. 313 (5794): 1781–4. Bibcode:2006Sci...313.1781M. doi:10.1126/science.1131864. PMID   16990547. S2CID   27127208.
  36. ↑ Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, Fraser G, Stalder AK, Beibel M, Staufenbiel M, Jucker M, Goedert M, Tolnay M (July 2009). "Transmission and spreading of tauopathy in transgenic mouse brain". Nature Cell Biology. 11 (7): 909–13. doi:10.1038/ncb1901. PMC   2726961 . PMID   19503072.
  37. ↑ Desplats P, Lee HJ, Bae EJ, Patrick C, Rockenstein E, Crews L, Spencer B, Masliah E, Lee SJ (August 2009). "Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein". Proceedings of the National Academy of Sciences of the United States of America. 106 (31): 13010–5. doi: 10.1073/pnas.0903691106 . PMC   2722313 . PMID   19651612.
  38. ↑ Hansen C, Angot E, Bergström AL, Steiner JA, Pieri L, Paul G, Outeiro TF, Melki R, Kallunki P, Fog K, Li JY, Brundin P (February 2011). "α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells". The Journal of Clinical Investigation. 121 (2): 715–25. doi:10.1172/JCI43366. PMC   3026723 . PMID   21245577.
  39. ↑ Kordower JH, Dodiya HB, Kordower AM, Terpstra B, Paumier K, Madhavan L, Sortwell C, Steece-Collier K, Collier TJ (September 2011). "Transfer of host-derived α synuclein to grafted dopaminergic neurons in rat". Neurobiology of Disease. 43 (3): 552–7. doi:10.1016/j.nbd.2011.05.001. PMC   3430516 . PMID   21600984.
  40. ↑ Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW (May 2008). "Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease". Nature Medicine. 14 (5): 504–6. doi:10.1038/nm1747. PMID   18391962. S2CID   11991816.
  41. ↑ Chia R, Tattum MH, Jones S, Collinge J, Fisher EM, Jackson GS (May 2010). Feany MB (ed.). "Superoxide dismutase 1 and tgSOD1 mouse spinal cord seed fibrils, suggesting a propagative cell death mechanism in amyotrophic lateral sclerosis". PLOS ONE. 5 (5): e10627. doi: 10.1371/journal.pone.0010627 . PMC   2869360 . PMID   20498711.
  42. ↑ Münch C, O'Brien J, Bertolotti A (March 2011). "Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells". Proceedings of the National Academy of Sciences of the United States of America. 108 (9): 3548–53. Bibcode:2011PNAS..108.3548M. doi: 10.1073/pnas.1017275108 . PMC   3048161 . PMID   21321227.
  43. ↑ Ren PH, Lauckner JE, Kachirskaia I, Heuser JE, Melki R, Kopito RR (February 2009). "Cytoplasmic penetration and persistent infection of mammalian cells by polyglutamine aggregates". Nature Cell Biology. 11 (2): 219–25. doi:10.1038/ncb1830. PMC   2757079 . PMID   19151706.
  44. ↑ Pearce MM, Kopito RR (February 2018). "Prion-Like Characteristics of Polyglutamine-Containing Proteins". Cold Spring Harbor Perspectives in Medicine. 8 (2): a024257. doi:10.1101/cshperspect.a024257. PMC   5793740 . PMID   28096245.
  45. ↑ Furukawa Y, Kaneko K, Watanabe S, Yamanaka K, Nukina N (May 2011). "A seeding reaction recapitulates intracellular formation of Sarkosyl-insoluble transactivation response element (TAR) DNA-binding protein-43 inclusions". The Journal of Biological Chemistry. 286 (21): 18664–72. doi: 10.1074/jbc.M111.231209 . PMC   3099683 . PMID   21454603.
  46. ↑ Lundmark K, Westermark GT, Olsén A, Westermark P (April 2005). "Protein fibrils in nature can enhance amyloid protein A amyloidosis in mice: Cross-seeding as a disease mechanism". Proceedings of the National Academy of Sciences of the United States of America. 102 (17): 6098–102. Bibcode:2005PNAS..102.6098L. doi: 10.1073/pnas.0501814102 . PMC   1087940 . PMID   15829582.
  47. ↑ Fu X, Korenaga T, Fu L, Xing Y, Guo Z, Matsushita T, Hosokawa M, Naiki H, Baba S, Kawata Y, Ikeda S, Ishihara T, Mori M, Higuchi K (April 2004). "Induction of AApoAII amyloidosis by various heterogeneous amyloid fibrils". FEBS Letters. 563 (1–3): 179–84. Bibcode:2004FEBSL.563..179F. doi: 10.1016/S0014-5793(04)00295-9 . PMID   15063745.
  48. ↑ Bolmont T, Clavaguera F, Meyer-Luehmann M, Herzig MC, Radde R, Staufenbiel M, Lewis J, Hutton M, Tolnay M, Jucker M (December 2007). "Induction of tau pathology by intracerebral infusion of amyloid-beta -containing brain extract and by amyloid-beta deposition in APP x Tau transgenic mice". The American Journal of Pathology. 171 (6): 2012–20. doi:10.2353/ajpath.2007.070403. PMC   2111123 . PMID   18055549.
  49. ↑ Morales R, Estrada LD, Diaz-Espinoza R, Morales-Scheihing D, Jara MC, Castilla J, Soto C (March 2010). "Molecular cross talk between misfolded proteins in animal models of Alzheimer's and prion diseases". The Journal of Neuroscience. 30 (13): 4528–35. doi:10.1523/JNEUROSCI.5924-09.2010. PMC   2859074 . PMID   20357103.
  50. 1 2 3 4 Revesz T, Ghiso J, Lashley T, Plant G, Rostagno A, Frangione B, Holton JL (September 2003). "Cerebral amyloid angiopathies: a pathologic, biochemical, and genetic view". Journal of Neuropathology and Experimental Neurology. 62 (9): 885–98. doi:10.1093/jnen/62.9.885. PMID   14533778.
  51. ↑ Guo L, Salt TE, Luong V, Wood N, Cheung W, Maass A, Ferrari G, Russo-Marie F, Sillito AM, Cheetham ME, Moss SE, Fitzke FW, Cordeiro MF (August 2007). "Targeting amyloid-beta in glaucoma treatment". Proceedings of the National Academy of Sciences of the United States of America. 104 (33): 13444–9. Bibcode:2007PNAS..10413444G. doi: 10.1073/pnas.0703707104 . PMC   1940230 . PMID   17684098.
  52. ↑ Prusiner, SB (2004). Prion Biology and Diseases (2 ed.). Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. ISBN   0-87969-693-1.
  53. ↑ Goedert M, Spillantini MG, Del Tredici K, Braak H (January 2013). "100 years of Lewy pathology". Nature Reviews. Neurology. 9 (1): 13–24. doi:10.1038/nrneurol.2012.242. PMID   23183883. S2CID   12590215.
  54. ↑ Clavaguera F, Hench J, Goedert M, Tolnay M (February 2015). "Invited review: Prion-like transmission and spreading of tau pathology". Neuropathology and Applied Neurobiology. 41 (1): 47–58. doi:10.1111/nan.12197. PMID   25399729. S2CID   45101893.
  55. 1 2 Mann DM, Snowden JS (November 2017). "Frontotemporal lobar degeneration: Pathogenesis, pathology and pathways to phenotype". Brain Pathology. 27 (6): 723–736. doi:10.1111/bpa.12486. PMC   8029341 . PMID   28100023.
  56. ↑ Grad LI, Fernando SM, Cashman NR (May 2015). "From molecule to molecule and cell to cell: prion-like mechanisms in amyotrophic lateral sclerosis". Neurobiology of Disease. 77: 257–65. doi:10.1016/j.nbd.2015.02.009. PMID   25701498. S2CID   18510138.
  57. ↑ Ludolph AC, Brettschneider J, Weishaupt JH (October 2012). "Amyotrophic lateral sclerosis". Current Opinion in Neurology. 25 (5): 530–5. doi:10.1097/WCO.0b013e328356d328. PMID   22918486.
  58. ↑ Orr HT, Zoghbi HY (July 2007). "Trinucleotide repeat disorders". Annual Review of Neuroscience. 30 (1): 575–621. doi:10.1146/annurev.neuro.29.051605.113042. PMID   17417937.
  59. ↑ Almeida B, Fernandes S, Abreu IA, Macedo-Ribeiro S (2013). "Trinucleotide repeats: a structural perspective". Frontiers in Neurology. 4: 76. doi: 10.3389/fneur.2013.00076 . PMC   3687200 . PMID   23801983.
  60. ↑ Spinner NB (March 2000). "CADASIL: Notch signaling defect or protein accumulation problem?". The Journal of Clinical Investigation. 105 (5): 561–2. doi:10.1172/JCI9511. PMC   292459 . PMID   10712425.
  61. ↑ Quinlan RA, Brenner M, Goldman JE, Messing A (June 2007). "GFAP and its role in Alexander disease". Experimental Cell Research. 313 (10): 2077–87. doi:10.1016/j.yexcr.2007.04.004. PMC   2702672 . PMID   17498694.
  62. ↑ Ito D, Suzuki N (January 2009). "Seipinopathy: a novel endoplasmic reticulum stress-associated disease". Brain. 132 (Pt 1): 8–15. doi: 10.1093/brain/awn216 . PMID   18790819.
  63. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 Sipe JD, Benson MD, Buxbaum JN, Ikeda SI, Merlini G, Saraiva MJ, Westermark P (December 2016). "Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines". Amyloid. 23 (4): 209–213. doi: 10.1080/13506129.2016.1257986 . PMID   27884064.
  64. ↑ Lomas DA, Carrell RW (October 2002). "Serpinopathies and the conformational dementias". Nature Reviews Genetics. 3 (10): 759–68. doi:10.1038/nrg907. PMID   12360234. S2CID   21633779.
  65. ↑ Mukherjee A, Soto C (May 2017). "Prion-Like Protein Aggregates and Type 2 Diabetes". Cold Spring Harbor Perspectives in Medicine. 7 (5): a024315. doi:10.1101/cshperspect.a024315. PMC   5411686 . PMID   28159831.
  66. ↑ Askanas V, Engel WK (January 2006). "Inclusion-body myositis: a myodegenerative conformational disorder associated with Abeta, protein misfolding, and proteasome inhibition". Neurology. 66 (2 Suppl 1): S39-48. doi:10.1212/01.wnl.0000192128.13875.1e. PMID   16432144. S2CID   24365234.
  67. ↑ Ecroyd H, Carver JA (January 2009). "Crystallin proteins and amyloid fibrils". Cellular and Molecular Life Sciences. 66 (1): 62–81. doi:10.1007/s00018-008-8327-4. PMC   11131532 . PMID   18810322. S2CID   6580402. Archived from the original on 2018-07-23. Retrieved 2021-09-15.
  68. ↑ Surguchev A, Surguchov A (January 2010). "Conformational diseases: looking into the eyes". Brain Research Bulletin. 81 (1): 12–24. doi:10.1016/j.brainresbull.2009.09.015. PMID   19808079. S2CID   38832894.
  69. ↑ Huilgol SC, Ramnarain N, Carrington P, Leigh IM, Black MM (May 1998). "Cytokeratins in primary cutaneous amyloidosis". The Australasian Journal of Dermatology. 39 (2): 81–5. doi:10.1111/j.1440-0960.1998.tb01253.x. PMID   9611375. S2CID   25820489.
  70. ↑ Janig E, Stumptner C, Fuchsbichler A, Denk H, Zatloukal K (March 2005). "Interaction of stress proteins with misfolded keratins". European Journal of Cell Biology. 84 (2–3): 329–39. doi:10.1016/j.ejcb.2004.12.018. PMID   15819411.
  71. ↑ D'Souza A, Theis JD, Vrana JA, Dogan A (June 2014). "Pharmaceutical amyloidosis associated with subcutaneous insulin and enfuvirtide administration". Amyloid. 21 (2): 71–5. doi:10.3109/13506129.2013.876984. PMC   4021035 . PMID   24446896.
  72. ↑ Meng X, Clews J, Kargas V, Wang X, Ford RC (January 2017). "The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability". Cellular and Molecular Life Sciences. 74 (1): 23–38. doi:10.1007/s00018-016-2386-8. PMC   5209436 . PMID   27734094.
  73. ↑ Stuart MJ, Nagel RL (2004). "Sickle-cell disease". Lancet. 364 (9442): 1343–60. doi:10.1016/S0140-6736(04)17192-4. PMID   15474138. S2CID   8139305.
  74. ↑ Bernstein AM, Ritch R, Wolosin JM (July 2018). "Exfoliation syndrome: A disease of autophagy and LOXL1 proteopathy". Journal of Glaucoma. 27 (Supplement 1): S44–S53. doi:10.1097/IJG.0000000000000919. PMC   6028293 . PMID   29547474.
  75. 1 2 3 Pepys MB (2006). "Amyloidosis". Annu Rev Med. 57: 223–241. doi:10.1146/annurev.med.57.121304.131243. PMID   16409147.
  76. 1 2 Holtzman DM, Morris JC, Goate AM (2011). "Alzheimer's disease: the challenge of the second century". Sci Transl Med. 3 (77): 77sr1. doi:10.1126/scitranslmed.3002369. PMC   3130546 . PMID   21471435.
  77. ↑ Pepys MB (2001). "Pathogenesis, diagnosis and treatment of systemic amyloidosis". Phil Trans R Soc Lond B. 356 (1406): 203–211. doi:10.1098/rstb.2000.0766. PMC   1088426 . PMID   11260801.
  78. ↑ Walker LC, LeVine H 3rd (2002). "Proteopathy: the next therapeutic frontier?". Curr Opin Investig Drugs. 3 (5): 782–7. PMID   12090553.
  79. ↑ Braczynski AK, Schulz JB, Bach JP (2017). "Vaccination strategies in tauopathies and synucleinopathies". J Neurochem. 143 (5): 467–488. doi: 10.1111/jnc.14207 . PMID   28869766.
  80. ↑ Klein WL (2013). "Synaptotoxic amyloid-β oligomers: a molecular basis for the cause, diagnosis, and treatment of Alzheimer's disease?". J Alzheimers Dis. 33 (Suppl 1): S49-65. doi:10.3233/JAD-2012-129039. PMID   22785404.
  81. 1 2 3 Badar T, D'Souza A, Hari P (2018). "Recent advances in understanding and treating immunoglobulin light chain amyloidosis". F1000Res. 7: 1348. doi: 10.12688/f1000research.15353.1 . PMC   6117860 . PMID   30228867.
  82. ↑ Carvalho A, Rocha A, Lobato L (2015). "Liver transplantation in transthyretin amyloidosis: issues and challenges". Liver Transpl. 21 (3): 282–292. doi: 10.1002/lt.24058 . PMID   25482846.
  83. ↑ Suhr OB, Herlenius G, Friman S, Ericzon BG (2000). "Liver transplantation for hereditary transthyretin amyloidosis". Liver Transpl. 6 (3): 263–276. doi: 10.1053/lv.2000.6145 . PMID   10827225.
  84. 1 2 Suhr OB, Larsson M, Ericzon BG, Wilczek HE, et al. (2016). "Survival After Transplantation in Patients With Mutations Other Than Val30Met: Extracts From the FAP World Transplant Registry". Transplantation. 100 (2): 373–381. doi:10.1097/TP.0000000000001021. PMC   4732012 . PMID   26656838.
  85. ↑ Coelho T, et al. (2016). "Mechanism of Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosis". Neurol Ther. 5 (1): 1–25. doi:10.1007/s40120-016-0040-x. PMC   4919130 . PMID   26894299.
  86. ↑ Yu D, et al. (2012). "Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression". Cell. 150 (5): 895–908. doi:10.1016/j.cell.2012.08.002. PMC   3444165 . PMID   22939619.
  87. ↑ Nuvolone M, Merlini G (2017). "Emerging therapeutic targets currently under investigation for the treatment of systemic amyloidosis". Expert Opin Ther Targets. 21 (12): 1095–1110. doi:10.1080/14728222.2017.1398235. PMID   29076382. S2CID   46766370.
  88. ↑ Joseph NS, Kaufman JL (2018). "Novel Approaches for the Management of AL Amyloidosis". Curr Hematol Malig Rep. 13 (3): 212–219. doi:10.1007/s11899-018-0450-1. PMID   29951831. S2CID   49475930.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.