Nerve tissue protein

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A nerve tissue protein is a biological molecule related to the function and maintenance of normal nervous tissue. [1] An example would include, for example, the generation of myelin which insulates and protects nerves. These are typically calcium-binding proteins.

Contents

Myelination and peripheral nervous system

There are two types of myelin. The first is oligodendrocyte, which can be found in the mammalian Central Nervous System (CNS). The second is Schwann cells, which are found in the Peripheral Nervous System (PNS). Myelination of axons by these Schwann cells are essential for normal nerve function. Peripheral nerves rely on communication between axons and Schwaan cells. [2]

Maintenance of myelin

Prion protein triggers are an important factor in the signals that ensure myelin maintenance and are distinct from those that direct myelination. Prion protein and antibodies POM1 and POM3, which recognize epitopes in the terminus (around amino acids (aa) 140–152) and charged clusters of prion protein (aa95-100) were used to their role in myelin maintenance. The result indicated that neuronal expression and regulated proteolysis of prion protein are essential for myelin maintenance.[ citation needed ]

Neurodegenerative disease

Neurodegenerative disease is caused by prions accumulation of PrPsc. The brains of humans or animals affected with prion disease show characteristics histopathological changes. However, the pathogenesis of the disease is largely unknown and treatment is often unsatisfactory. Tests on 60-week-old mice investigated PrPc – deficient mice showed chronic demyelinating polyneuropathy. Chronic demyelinating polyneuropathy was 100% penetrant and conspicuous in all investigated peripheral nerves. Large fibers we affected in axons when morphometry was used and identical pathologies were detected in the sciatic nerves. [3]

Proteins

Neuronal apoptosis inhibitory protein

Neuronal apoptosis inhibitory protein (NAIP) belongs to the family of proteins called the inhibitor of apoptosis family (IAP), these proteins are one of the key regulators of apoptosis. However, when NAIP use baculovirus IAP-repeat (BIR) domains to interact with caspases, they inhibit otherwise automatic formation of procaspase-9, an apoptosis initiator. [4]

The three-dimensional structure of all BIR domains is constructed of two to three NH2-terminus α-helices, a central antiparallel β-sheet, and two to three carboxy-terminus α-¬helices. IAP-binding motifs (IBMs) are constructed from amino-terminal tetrapeptides. The binding sites of the IBMs are between the last strand of the β-sheet and the nearby α-¬helix. The zinc ion is chelated by one histidine and three cysteines. The NH2-terminus serine binds to IBM-binding groove, P1’. The serine chain (S) is inserted into an amino acid hydrophobic pocket. Once in this pocket, hydrogen bonds attach to the oxygen atom of the serine chain, also the oxygen atom at P1’ forms another hydrogen bond to the tryptophan chain. The tryptophan chain also interacts with the carbon atoms of the arginine at P3’. A backbone of nitrogen and oxygen at P2’ and of nitrogen at P4’ provide stability. [5]

When coexpressed, the presence of both NAIP and hippocalcin caused neuroblastoma cells to be protected from cell death through the induction of increased calcium levels. [5]

NAIP has been shown to be involved in the inherited disease spinal muscular atrophy. The interaction between NAIP and hippocalcin, a neuronal calcium-sensor protein, has been observed to take place in the zinc-binding region along with other specific amino acids. In sympathetic neurons, the expression of NAIP-BIR3 and hippocalcin did not provide any significant protection from cell death from the withdrawal of nerve growth factor. This is unexpected because, in nerve growth factor withdrawal, caspase-3 and -9 are activated, causing cell death, which are the very caspases blocked by NAIP. [4]

Hippocalcin

Hippocalcin is a neuronal calcium-sensor protein which has two to three regions that can bind with calcium ions. [5]

XIAP

The X-linked IAP (XIAP) is an extremely powerful inhibitor of apoptosis. This is done through the binding to caspases directly. Similar to the functionality of NAIP, the BIR3 domain of XIAP binds to the carboxyl-terminal subunit of caspase-9. Between S1 and S1’ is where the catalysis occurs. In caspase-3 the ‘hook’ and ‘sinker’ attach. Both the BIR2 and BIR3 have a groove that is predominately negatively charged. This negative charge in BIR3 allows the attachment of the IAP-binding motif, causing enzymatic activity to be inhibited. [6]
When overexpressed, XIAP is able to block caspases extremely well and prevents cell death of sympathetic neurons when nerve growth factors are deprived. [7]

Types

Related Research Articles

<span class="mw-page-title-main">Axon</span> Long projection on a neuron that conducts signals to other neurons

An axon or nerve fiber is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons, such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the periphery to the cell body and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction can be the cause of many inherited and acquired neurological disorders that affect both the peripheral and central neurons. Nerve fibers are classed into three types – group A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated, and group C are unmyelinated. These groups include both sensory fibers and motor fibers. Another classification groups only the sensory fibers as Type I, Type II, Type III, and Type IV.

<span class="mw-page-title-main">Neuron</span> Electrically excitable cell found in the nervous system of animals

A neuron, neurone, or nerve cell is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. Neurons communicate with other cells via synapses, which are specialized connections that commonly use minute amounts of chemical neurotransmitters to pass the electric signal from the presynaptic neuron to the target cell through the synaptic gap.

<span class="mw-page-title-main">Schwann cell</span> Glial cell type

Schwann cells or neurolemmocytes are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensheathing cells, enteric glia and glia that reside at sensory nerve endings, such as the Pacinian corpuscle. The two types of Schwann cells are myelinating and nonmyelinating. Myelinating Schwann cells wrap around axons of motor and sensory neurons to form the myelin sheath. The Schwann cell promoter is present in the downstream region of the human dystrophin gene that gives shortened transcript that are again synthesized in a tissue-specific manner.

<span class="mw-page-title-main">Excitatory synapse</span> Sort of synapse

An excitatory synapse is a synapse in which an action potential in a presynaptic neuron increases the probability of an action potential occurring in a postsynaptic cell. Neurons form networks through which nerve impulses travels, each neuron often making numerous connections with other cells of neurons. These electrical signals may be excitatory or inhibitory, and, if the total of excitatory influences exceeds that of the inhibitory influences, the neuron will generate a new action potential at its axon hillock, thus transmitting the information to yet another cell.

<span class="mw-page-title-main">Wallerian degeneration</span> Biological process of axonal degeneration

Wallerian degeneration is an active process of degeneration that results when a nerve fiber is cut or crushed and the part of the axon distal to the injury degenerates. A related process of dying back or retrograde degeneration known as 'Wallerian-like degeneration' occurs in many neurodegenerative diseases, especially those where axonal transport is impaired such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. Primary culture studies suggest that a failure to deliver sufficient quantities of the essential axonal protein NMNAT2 is a key initiating event.

<span class="mw-page-title-main">Peripherin</span> Protein-coding gene in the species Homo sapiens

Peripherin is a type III intermediate filament protein expressed mainly in neurons of the peripheral nervous system. It is also found in neurons of the central nervous system that have projections toward peripheral structures, such as spinal motor neurons. Its size, structure, and sequence/location of protein motifs is similar to other type III intermediate filament proteins such as desmin, vimentin and glial fibrillary acidic protein. Like these proteins, peripherin can self-assemble to form homopolymeric filamentous networks, but it can also heteropolymerize with neurofilaments in several neuronal types. This protein in humans is encoded by the PRPH gene. Peripherin is thought to play a role in neurite elongation during development and axonal regeneration after injury, but its exact function is unknown. It is also associated with some of the major neuropathologies that characterize amyotropic lateral sclerosis (ALS), but despite extensive research into how neurofilaments and peripherin contribute to ALS, their role in this disease is still unidentified.

<span class="mw-page-title-main">Soma (biology)</span> Portion of a brain cell containing its nucleus

In cellular neuroscience, the soma, perikaryon, neurocyton, or cell body is the bulbous, non-process portion of a neuron or other brain cell type, containing the cell nucleus. Although it is often used to refer to neurons, it can also refer to other cell types as well, including astrocytes, oligodendrocytes, and microglia. There are many different specialized types of neurons, and their sizes vary from as small as about 5 micrometres to over 10 millimetres for some of the smallest and largest neurons of invertebrates, respectively.

<span class="mw-page-title-main">Low-affinity nerve growth factor receptor</span> Human protein-coding gene

The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic factor receptor. Neurotrophic factor receptors bind Neurotrophins including Nerve growth factor, Neurotrophin-3, Brain-derived neurotrophic factor, and Neurotrophin-4. All neurotrophins bind to p75NTR. This also includes the immature pro-neurotrophin forms. Neurotrophic factor receptors, including p75NTR, are responsible for ensuring a proper density to target ratio of developing neurons, refining broader maps in development into precise connections. p75NTR is involved in pathways that promote neuronal survival and neuronal death.

<span class="mw-page-title-main">Hippocalcin</span> Protein-coding gene in the species Homo sapiens

Hippocalcin is a protein that in humans is encoded by the HPCA gene.

<span class="mw-page-title-main">Nerve injury</span> Damage to nervous tissue

Nerve injury is an injury to a nerve. There is no single classification system that can describe all the many variations of nerve injuries. In 1941, Seddon introduced a classification of nerve injuries based on three main types of nerve fiber injury and whether there is continuity of the nerve. Usually, however, nerve injuries are classified in five stages, based on the extent of damage to both the nerve and the surrounding connective tissue, since supporting glial cells may be involved.

Inhibitors of apoptosis are a group of proteins that mainly act on the intrinsic pathway that block programmed cell death, which can frequently lead to cancer or other effects for the cell if mutated or improperly regulated. Many of these inhibitors act to block caspases, a family of cysteine proteases that play an integral role in apoptosis. Some of these inhibitors include the Bcl-2 family, viral inhibitor crmA, and IAP's.

Neuroregeneration is the regrowth or repair of nervous tissues, cells or cell products. Neuroregenerative mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous system (PNS) and the central nervous system (CNS) by the functional mechanisms involved, especially in the extent and speed of repair. When an axon is damaged, the distal segment undergoes Wallerian degeneration, losing its myelin sheath. The proximal segment can either die by apoptosis or undergo the chromatolytic reaction, which is an attempt at repair. In the CNS, synaptic stripping occurs as glial foot processes invade the dead synapse.

<span class="mw-page-title-main">XIAP</span> Protein-coding gene in the species Homo sapiens

X-linked inhibitor of apoptosis protein (XIAP), also known as inhibitor of apoptosis protein 3 (IAP3) and baculoviral IAP repeat-containing protein 4 (BIRC4), is a protein that stops apoptotic cell death. In humans, this protein (XIAP) is produced by a gene named XIAP gene located on the X chromosome.

<span class="mw-page-title-main">Baculoviral IAP repeat-containing protein 3</span> Protein-coding gene in the species Homo sapiens

Baculoviral IAP repeat-containing protein3 is a protein that in humans is encoded by the BIRC3 gene.

<span class="mw-page-title-main">Baculoviral IAP repeat-containing protein 2</span> Protein-coding gene in the species Homo sapiens

Baculoviral IAP repeat-containing protein 2 is a protein that in humans is encoded by the BIRC2 gene.

<span class="mw-page-title-main">Diablo homolog</span> Protein-coding gene in the species Homo sapiens

Diablo homolog (DIABLO) is a mitochondrial protein that in humans is encoded by the DIABLO gene on chromosome 12. DIABLO is also referred to as second mitochondria-derived activator of caspases or SMAC. This protein binds inhibitor of apoptosis proteins (IAPs), thus freeing caspases to activate apoptosis. Due to its proapoptotic function, SMAC is implicated in a broad spectrum of tumors, and small molecule SMAC mimetics have been developed to enhance current cancer treatments.

<span class="mw-page-title-main">Serine protease HTRA2, mitochondrial</span> Enzyme found in humans

Serine protease HTRA2, mitochondrial is an enzyme that in humans is encoded by the HTRA2 gene. This protein is involved in caspase-dependent apoptosis and in Parkinson's disease.

<span class="mw-page-title-main">NAIP (gene)</span> Protein and coding gene in humans

Baculoviral IAP repeat-containing protein 1 is a protein that in humans is encoded by the NAIP gene.

<span class="mw-page-title-main">LINGO1</span> Protein-coding gene in the species Homo sapiens

Leucine-rich repeat and Immunoglobulin-like domain-containing protein 1 also known as LINGO-1 is a protein which is encoded by the LINGO1 gene in humans. It belongs to the family of leucine-rich repeat proteins which are known for playing key roles in the biology of the central nervous system. LINGO-1 is a functional component of the Nogo receptor also known as the reticulon 4 receptor.

<span class="mw-page-title-main">Chromatolysis</span> Dissolution of a neurons Nissl bodies

In cellular neuroscience, chromatolysis is the dissolution of the Nissl bodies in the cell body of a neuron. It is an induced response of the cell usually triggered by axotomy, ischemia, toxicity to the cell, cell exhaustion, virus infections, and hibernation in lower vertebrates. Neuronal recovery through regeneration can occur after chromatolysis, but most often it is a precursor of apoptosis. The event of chromatolysis is also characterized by a prominent migration of the nucleus towards the periphery of the cell and an increase in the size of the nucleolus, nucleus, and cell body. The term "chromatolysis" was initially used in the 1940s to describe the observed form of cell death characterized by the gradual disintegration of nuclear components; a process which is now called apoptosis. Chromatolysis is still used as a term to distinguish the particular apoptotic process in the neuronal cells, where Nissl substance disintegrates.

References

  1. 1 2 Nerve+tissue+proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  2. ↑ Raiker, S. J.; Lee, H.; Baldwin, K. T.; Duan, Y.; Shrager, P.; Giger, R. J. (2010). "Oligodendrocyte-Myelin Glycoprotein and Nogo Negatively Regulate Activity-Dependent Synaptic Plasticity". Journal of Neuroscience. 30 (37): 12432–45. doi:10.1523/JNEUROSCI.0895-10.2010. PMC   2967212 . PMID   20844138.
  3. ↑ Bremer, Juliane; Baumann, Frank; Tiberi, Cinzia; Wessig, Carsten; Fischer, Heike; Schwarz, Petra; Steele, Andrew D; Toyka, Klaus V; et al. (2010). "Axonal prion protein is required for peripheral myelin maintenance". Nature Neuroscience. 13 (3): 310–8. doi:10.1038/nn.2483. PMID   20098419. S2CID   205432942.
  4. 1 2 Herman, Maria Dolores; Moche, Martin; Flodin, Susanne; Welin, Martin; Trésaugues, Lionel; Johansson, Ida; Nilsson, Martina; Nordlund, Pär; Nyman, Tomas (2009). "Structures of BIR domains from human NAIP and cIAP2". Acta Crystallographica. 65 (11): 1091–6. doi:10.1107/S1744309109038597. PMC   2777033 . PMID   19923725.
  5. 1 2 3 Mercer, E. A.; Korhonen, L; Skoglösa, Y; Olsson, PA; Kukkonen, JP; Lindholm, D (2000). "NAIP interacts with hippocalcin and protects neurons against calcium-induced cell death through caspase-3-dependent and -independent pathways". The EMBO Journal. 19 (14): 3597–607. doi:10.1093/emboj/19.14.3597. PMC   313967 . PMID   10899114.
  6. ↑ Salvesen, Guy S.; Duckett, Colin S. (2002). "Apoptosis: IAP proteins: Blocking the road to death's door". Nature Reviews Molecular Cell Biology. 3 (6): 401–10. doi:10.1038/nrm830. PMID   12042762. S2CID   15238683.
  7. ↑ Lindholm, Dan; Mercer, Eric A; Yu, Li-Ying; Chen, Yuming; Kukkonen, Jyrki; Korhonen, Laura; Arumäe, Urmas (2002). "Neuronal apoptosis inhibitory protein: Structural requirements for hippocalcin binding and effects on survival of NGF-dependent sympathetic neurons". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1600 (1–2): 138–47. doi:10.1016/S1570-9639(02)00454-5. PMID   12445469.
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