PINK1

Last updated
PINK1
Identifiers
Aliases PINK1 , BRPK, PARK6, PTEN induced putative kinase 1, PTEN induced kinase 1
External IDs OMIM: 608309 MGI: 1916193 HomoloGene: 32672 GeneCards: PINK1
Orthologs
SpeciesHumanMouse
Entrez

65018

68943

Ensembl

ENSG00000158828

ENSMUSG00000028756

UniProt

Q9BXM7

Q99MQ3

RefSeq (mRNA)

NM_032409

NM_026880

RefSeq (protein)

NP_115785

NP_081156

Location (UCSC) Chr 1: 20.63 – 20.65 Mb Chr 4: 138.04 – 138.05 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

PTEN-induced kinase 1 (PINK1) is a mitochondrial serine/threonine-protein kinase encoded by the PINK1 gene. [5] [6]

Contents

It is thought to protect cells from stress-induced mitochondrial dysfunction. PINK1 activity causes the parkin protein to bind to depolarized mitochondria to induce autophagy of those mitochondria. [7] [8] PINK1 is processed by healthy mitochondria and released to trigger neuron differentiation. [9] Mutations in this gene cause one form of autosomal recessive early-onset Parkinson's disease. [10]

Structure

PINK1 is synthesized as a 63000 Da protein which is often cleaved by PARL, between the 103-Alanine and the 104-Phenylalanine residues, into a 53000 Da fragment. [11] PINK1 contains an N-terminal mitochondrial localization sequence, a putative transmembrane sequence, a Ser/Thr kinase domain, and a C-terminal regulatory sequence. The protein has been found to localize to the outer membrane of mitochondria, but can also be found throughout the cytosol. Experiments suggest the Ser/Thr kinase domain faces outward toward the cytosol, indicating a possible point of interaction with parkin. [12]

The structure of PINK1 has been solved and shows how the protein binds and phosphorylates its substrate ubiquitin. [13]

Function

PINK1 is intimately involved with mitochondrial quality control by identifying damaged mitochondria and targeting specific mitochondria for degradation. Healthy mitochondria maintain a membrane potential that can be used to import PINK1 into the inner membrane where it is cleaved by PARL and cleared from the outer membrane. Severely damaged mitochondria lack sufficient membrane potential to import PINK1, which then accumulates on the outer membrane. PINK1 then recruits parkin to target the damaged mitochondria for degradation through autophagy. [14] Due to the presence of PINK1 throughout the cytoplasm, it has been suggested that PINK1 functions as a "scout" to probe for damaged mitochondria. [15]

Damaged mitochondria is being recognized by PINK1. PINK1 builds up on the outer membrane of the mitochondria and recruits parkin. The PINK1/parkin pathway then designates the mitochondria for degradation by lysosomes. Degradation of damaged mitochondria with PINK1.png
Damaged mitochondria is being recognized by PINK1. PINK1 builds up on the outer membrane of the mitochondria and recruits parkin. The PINK1/parkin pathway then designates the mitochondria for degradation by lysosomes.
Healthy mitochondria can import PINK1 where it is subsequently cleaved by PARL. This prevents any buildup of PINK1 and parkin is not recruited to the mitochondria. PINK1 with healthy mitochondria.png
Healthy mitochondria can import PINK1 where it is subsequently cleaved by PARL. This prevents any buildup of PINK1 and parkin is not recruited to the mitochondria.

PINK1 may also control mitochondria quality through mitochondrial fission. Through mitochondrial fission, a number of daughter mitochondria are created, often with an uneven distribution in membrane potential. Mitochondria with a strong, healthy membrane potential were more likely to undergo fusion than mitochondria with low membrane potential. Interference with the mitochondrial fission pathway led to an increase in oxidized proteins and a decrease in respiration. [16] Without PINK1, parkin cannot efficiently localize to damaged mitochondria, while an over-expression of PINK1 causes parkin to localize to even healthy mitochondria. [17] Furthermore, mutations in both Drp1, a mitochondrial fission factor, and PINK1 were fatal in Drosophila models. However, an over-expression of Drp1 could rescue subjects deficient in PINK1 or parkin, suggesting mitochondrial fission initiated by Drp1 recreates the same effects of the PINK1/parkin pathway. [18]

In addition to mitochondrial fission, PINK1 has been implicated in mitochondrial motility. The accumulation of PINK1 and recruitment of parkin targets a mitochondrion for degradation, and PINK1 may serve to enhance degradation rates by arresting mitochondrial motility. Over-expression of PINK1 produced similar effects to silencing Miro, a protein closely associated with mitochondrial migration. [19]

Another mechanism of mitochondrial quality control may arise through mitochondria-derived vesicles. Oxidative stress in mitochondria can produce potentially harmful compounds including improperly folded proteins or reactive oxygen species. PINK1 has been shown to facilitate the creation of mitochondria-derived vesicles which can separate reactive oxygen species and shuttle them toward lysosomes for degradation. [20]

Disease relevance

Parkinson's disease is often characterized by the degeneration of dopaminergic neurons and associated with the build-up of improperly folded proteins and Lewy bodies. Mutations in the PINK1 protein have been shown to lead to a build-up of such improperly folded proteins in the mitochondria of both fly and human cells. [21] Specifically, mutations in the serine/threonine kinase domain have been found in a number of Parkinson's patients where PINK1 fails to protect against stress-induced mitochondrial dysfunction and apoptosis. [22]

Pharmacological manipulation

To date, there have been few reports of small molecules that activate PINK1 and their promise as potential treatments for Parkinson's disease. The first report appeared in 2013 when Kevan Shokat and his team from UCSF identified a nucleobase called kinetin as an activator of PINK1. [23] Subsequently, it was shown by others that the nucleoside derivative of kinetin, i.e. kinetin riboside, exhibited significant activation of PINK1 in cells. [24] Additionally, the monophosphate prodrugs of kinetin riboside, ProTides, also showed activation of PINK1. [25] In December 2017, niclosamide, an anthelmintic drug, was identified as a potent activator of PINK1 in cells and in neurons. [26]

Related Research Articles

<span class="mw-page-title-main">Mitochondrion</span> Organelle in eukaryotic cells responsible for respiration

A mitochondrion is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used throughout the cell as a source of chemical energy. They were discovered by Albert von Kölliker in 1857 in the voluntary muscles of insects. The term mitochondrion was coined by Carl Benda in 1898. The mitochondrion is popularly nicknamed the "powerhouse of the cell", a phrase coined by Philip Siekevitz in a 1957 article of the same name.

<span class="mw-page-title-main">Parkin (protein)</span>

Parkin is a 465-amino acid residue E3 ubiquitin ligase, a protein that in humans and mice is encoded by the PARK2 gene. Parkin plays a critical role in ubiquitination – the process whereby molecules are covalently labelled with ubiquitin (Ub) and directed towards degradation in proteasomes or lysosomes. Ubiquitination involves the sequential action of three enzymes. First, an E1 ubiquitin-activating enzyme binds to inactive Ub in eukaryotic cells via a thioester bond and mobilises it in an ATP-dependent process. Ub is then transferred to an E2 ubiquitin-conjugating enzyme before being conjugated to the target protein via an E3 ubiquitin ligase. There exists a multitude of E3 ligases, which differ in structure and substrate specificity to allow selective targeting of proteins to intracellular degradation.

<span class="mw-page-title-main">Human mitochondrial genetics</span> Study of the human mitochondrial genome

Human mitochondrial genetics is the study of the genetics of human mitochondrial DNA. The human mitochondrial genome is the entirety of hereditary information contained in human mitochondria. Mitochondria are small structures in cells that generate energy for the cell to use, and are hence referred to as the "powerhouses" of the cell.

<span class="mw-page-title-main">LRRK2</span> Protein kinase found in humans

Leucine-rich repeat kinase 2 (LRRK2), also known as dardarin and PARK8, is a large, multifunctional kinase enzyme that in humans is encoded by the LRRK2 gene. LRRK2 is a member of the leucine-rich repeat kinase family. Variants of this gene are associated with an increased risk of Parkinson's disease and Crohn's disease.

<span class="mw-page-title-main">MFN2</span> Protein-coding gene in the species Homo sapiens

Mitofusin-2 is a protein that in humans is encoded by the MFN2 gene. Mitofusins are GTPases embedded in the outer membrane of the mitochondria. In mammals MFN1 and MFN2 are essential for mitochondrial fusion. In addition to the mitofusins, OPA1 regulates inner mitochondrial membrane fusion, and DRP1 is responsible for mitochondrial fission.

<span class="mw-page-title-main">TIMM8A</span> Protein-coding gene in humans

Mitochondrial import inner membrane translocase subunit Tim8 A, also known as deafness-dystonia peptide or protein is an enzyme that in humans is encoded by the TIMM8A gene. This translocase has similarity to yeast mitochondrial proteins that are involved in the import of metabolite transporters from the cytoplasm into the mitochondrial inner membrane. The gene is mutated in deafness-dystonia syndrome and it is postulated that MTS/DFN-1 is a mitochondrial disease caused by a defective mitochondrial protein import system.

<span class="mw-page-title-main">VPS35</span> Protein-coding gene in the species Homo sapiens

Vacuolar protein sorting ortholog 35 (VPS35) is a protein involved in autophagy and is implicated in neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). VPS35 is part of a complex called the retromer, which is responsible for transporting select cargo proteins between vesicular structures and the Golgi apparatus. Mutations in the VPS35 gene (VPS35) cause aberrant autophagy, where cargo proteins fail to be transported and dysfunctional or unnecessary proteins fail to be degraded. There are numerous pathways affected by altered VPS35 levels and activity, which have clinical significance in neurodegeneration. There is therapeutic relevance for VPS35, as interventions aimed at correcting VPS35 function are in speculation.

<span class="mw-page-title-main">RHOT1</span> Protein-coding gene in the species Homo sapiens

Mitochondrial Rho GTPase 1 (MIRO1) is an enzyme that in humans is encoded by the RHOT1 gene on chromosome 17. As a Miro protein isoform, the protein facilitates mitochondrial transport by attaching the mitochondria to the motor/adaptor complex. Through its key role in mitochondrial transport, RHOT1 is involved in mitochondrial homeostasis and apoptosis, as well as Parkinson’s disease (PD) and cancer.

<span class="mw-page-title-main">RHOT2</span> Protein-coding gene in the species Homo sapiens

Mitochondrial Rho GTPase 2 is an enzyme that in humans is encoded by the RHOT2 gene. As a Miro protein isoform, the protein facilitates mitochondrial transport by attaching the mitochondria to the motor/adaptor complex. Through its key role in mitochondrial transport, RHOT2 is involved in mitochondrial homeostasis and apoptosis, as well as Parkinson’s disease (PD).

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

Presenilins-associated rhomboid-like protein, mitochondrial (PSARL), also known as PINK1/PGAM5-associated rhomboid-like protease (PARL), is an inner mitochondrial membrane protein that in humans is encoded by the PARL gene on chromosome 3. It is a member of the rhomboid family of intramembrane serine proteases. This protein is involved in signal transduction and apoptosis, as well as neurodegenerative diseases and type 2 diabetes.

<span class="mw-page-title-main">VDAC3</span> Protein-coding gene in the species Homo sapiens

Voltage-dependent anion-selective channel protein 3 (VDAC3) is a protein that in humans is encoded by the VDAC3 gene on chromosome 8. The protein encoded by this gene is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoforms. Nonetheless, VDAC3 demonstrates limited pore-forming ability and, instead, interacts with other proteins to perform its biological functions, including sperm flagella assembly and centriole assembly. Mutations in VDAC3 have been linked to male infertility, as well as Parkinson’s disease.

Mitophagy is the selective degradation of mitochondria by autophagy. It often occurs to defective mitochondria following damage or stress. The process of mitophagy was first described over a hundred years ago by Margaret Reed Lewis and Warren Harmon Lewis. Ashford and Porter used electron microscopy to observe mitochondrial fragments in liver lysosomes by 1962, and a 1977 report suggested that "mitochondria develop functional alterations which would activate autophagy." The term "mitophagy" was in use by 1998.

Parkinson's disease (PD) is a degenerative disorder of the central nervous system. Most people with PD have idiopathic Parkinson's disease. A small proportion of cases, however, can be attributed to known genetic factors. Other factors such as environmental toxins, herbicides, pesticides, and fungicides, have been associated with the risk of developing PD, but no causal relationships have been proven.

<span class="mw-page-title-main">Mitochondrial fusion</span> Merging of two or more mitochondria within a cell to form a single compartment

Mitochondria are dynamic organelles with the ability to fuse and divide (fission), forming constantly changing tubular networks in most eukaryotic cells. These mitochondrial dynamics, first observed over a hundred years ago are important for the health of the cell, and defects in dynamics lead to genetic disorders. Through fusion, mitochondria can overcome the dangerous consequences of genetic malfunction. The process of mitochondrial fusion involves a variety of proteins that assist the cell throughout the series of events that form this process.

<span class="mw-page-title-main">MUL1</span> Protein-coding gene in the species Homo sapiens

Mitochondrial E3 ubiquitin protein ligase 1 (MUL1) is an enzyme that in humans is encoded by the MUL1 gene on chromosome 1. This enzyme localizes to the outer mitochondrial membrane, where it regulates mitochondrial morphology and apoptosis through multiple pathways, including the Akt, JNK, and NF-κB. Its proapoptotic function thus implicates it in cancer and Parkinson’s disease.

<span class="mw-page-title-main">Pathophysiology of Parkinson's disease</span> Medical condition

The pathophysiology of Parkinson's disease is death of dopaminergic neurons as a result of changes in biological activity in the brain with respect to Parkinson's disease (PD). There are several proposed mechanisms for neuronal death in PD; however, not all of them are well understood. Five proposed major mechanisms for neuronal death in Parkinson's Disease include protein aggregation in Lewy bodies, disruption of autophagy, changes in cell metabolism or mitochondrial function, neuroinflammation, and blood–brain barrier (BBB) breakdown resulting in vascular leakiness.

<span class="mw-page-title-main">Mitochondria associated membranes</span> Cellular structure

Mitochondria-associated membranes (MAM) represent a region of the endoplasmic reticulum (ER) which is reversibly tethered to mitochondria. These membranes are involved in import of certain lipids from the ER to mitochondria and in regulation of calcium homeostasis, mitochondrial function, autophagy and apoptosis. They also play a role in development of neurodegenerative diseases and glucose homeostasis.

<span class="mw-page-title-main">SLC25A46</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 25 member 46 is a protein that in humans is encoded by the SLC25A46 gene. This protein is a member of the SLC25 mitochondrial solute carrier family. It is a transmembrane protein located in the mitochondrial outer membrane involved in lipid transfer from the endoplasmic reticulum (ER) to mitochondria. Mutations in this gene result in neuropathy and optic atrophy.

Miratul Muqit FRSE FMedSci is a British neurologist and a Programme Lead at the MRC Protein Phosphorylation and Ubiquitylation Unit (MRCPPU) in the School of Life Sciences at the University of Dundee. His research focuses on the study of the PINK1 gene, mutations in which are a major cause of Parkinson's disease.

<span class="mw-page-title-main">Animal models of Parkinson's disease</span> Models used in Parkinsons disease research

Animal models of Parkinson's disease are essential in the research field and widely used to study Parkinson's disease. Parkinson's disease is a neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The loss of the dopamine neurons in the brain, results in motor dysfunction, ultimately causing the four cardinal symptoms of PD: tremor, rigidity, postural instability, and bradykinesia. It is the second most prevalent neurodegenerative disease, following Alzheimer's disease. It is estimated that nearly one million people could be living with PD in the United States.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000158828 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028756 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Unoki M, Nakamura Y (Aug 2001). "Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway". Oncogene. 20 (33): 4457–65. doi: 10.1038/sj.onc.1204608 . PMID   11494141.
  6. ↑ Valente EM, Salvi S, Ialongo T, Marongiu R, Elia AE, Caputo V, Romito L, Albanese A, Dallapiccola B, Bentivoglio AR (Sep 2004). "PINK1 mutations are associated with sporadic early-onset parkinsonism". Ann Neurol. 56 (3): 336–41. doi:10.1002/ana.20256. PMID   15349860. S2CID   11049051.
  7. ↑ Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ (2010). "PINK1 is selectively stabilized on impaired mitochondria to activate Parkin". PLOS Biology . 8 (1): e1000298. doi: 10.1371/journal.pbio.1000298 . PMC   2811155 . PMID   20126261.
  8. ↑ Lazarou M, Narendra DP, Jin SM, Tekle E, Banerjee S, Youle RJ (2013). "PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding". Journal of Cell Biology . 200 (2): 163–172. doi:10.1083/jcb.201210111. PMC   3549971 . PMID   23319602.
  9. ↑ Dagda RK, Pien I, Wang R, Zhu J, Wang KZ, Callio J, Banerjee TD, Dagda RY, Chu CT (2013). "Beyond the mitochondrion: cytosolic PINK1 remodels dendrites through protein kinase A". J Neurochem . 128 (6): 864–877. doi:10.1111/jnc.12494. PMC   3951661 . PMID   24151868.
  10. ↑ "Entrez Gene: PINK1 PTEN induced putative kinase 1".
  11. ↑ Deas E, Plun-Favreau H, Gandhi S, Desmond H, Kjaer S, Loh SH, Renton AE, Harvey RJ, Whitworth AJ, Martins LM, Abramov AY, Wood NW (2011). "PINK1 cleavage at position A103 by the mitochondrial protease PARL". Hum. Mol. Genet. 20 (5): 867–869. doi:10.1093/hmg/ddq526. PMC   3033179 . PMID   21138942.
  12. ↑ Springer W, Kahle PJ (March 2011). "Regulation of PINK1-Parkin-mediated mitophagy". Autophagy. 7 (3): 266–78. doi:10.4161/auto.7.3.14348. PMID   21187721. S2CID   31612944.
  13. ↑ Schubert AF, Gladkova C, Pardon E, Wagstaff JL, Freund SM, Steyaert J, Maslen SL, Komander D (2017-10-30). "Structure of PINK1 in complex with its substrate ubiquitin". Nature. 552 (7683): 51–56. Bibcode:2017Natur.552...51S. doi:10.1038/nature24645. ISSN   1476-4687. PMC   6020998 . PMID   29160309.
  14. ↑ Youle RJ, van der Bliek AM (2012). "Mitochondrial fission, fusion, and stress". Science. 337 (6098): 1062–1065. Bibcode:2012Sci...337.1062Y. doi:10.1126/science.1219855. PMC   4762028 . PMID   22936770.
  15. ↑ Narendra D, Walker JE, Youle R (2012). "Mitochondrail quality control mediated by PINK1 and Parkin: links to parkinsonism". Cold Spring Harbor Perspectives in Biology. 4 (11): a011338. doi:10.1101/cshperspect.a011338. PMC   3536340 . PMID   23125018.
  16. ↑ Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G, Alroy J, Wu M, Py BF, Yuan J, Deeney JT, Corkey BE, Shirihai OS (2008). "Fission and selective fusion govern mitochondrial segregation and elimination by autophagy". The EMBO Journal. 27 (2): 433–446. doi:10.1038/sj.emboj.7601963. PMC   2234339 . PMID   18200046.
  17. ↑ Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, May J, Tocilescu MA, Liu W, Ko HS, Magrané J, Moore DJ, Dawson VL, Grailhe R, Dawson TM, Li C, Tieu K, Przedborski S (2010). "PINK1-dependent recruitment of Parkin to mitochondria in mitophagy". Proceedings of the National Academy of Sciences of the United States of America. 107 (1): 378–83. Bibcode:2010PNAS..107..378V. doi: 10.1073/pnas.0911187107 . PMC   2806779 . PMID   19966284.
  18. ↑ Poole AC, Thomas RE, Andrews LA, McBride HM, Whitworth AJ, Pallanck LJ (2008). "The PINK1/Parkin pathway regulates mitochondrial mitophagy". Proceedings of the National Academy of Sciences of the United States of America. 105 (5): 1638–43. doi: 10.1073/pnas.0709336105 . PMC   2234197 . PMID   18230723.
  19. ↑ Liu S, Sawada T, Lee S, Yu W, Silverio G, Alapatt P, Millan I, Shen A, Saxton W, Kanao T, Takahashi R, Hattori N, Imai Y, Lu B (2012). "Parkinson's disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria". PLOS Genetics. 8 (3): e102537. doi: 10.1371/journal.pgen.1002537 . PMC   3291531 . PMID   22396657.
  20. ↑ McLelland GL, Soubannier V, Chen CX, McBride HM, Fon EA (2014). "Parkin and PINK 1 function in a vesicular trafficking pathway regulating mitochondrial quality control". The EMBO Journal. 33 (4): 282–295. doi:10.1002/embj.201385902. PMC   3989637 . PMID   24446486.
  21. ↑ Pimenta de Castro I, Costa AC, Lam D, Tufi R, Fedele V, Moisoi N, Dinsdale D, Deas E, Loh SH, Martins LM (2012). "Genetic analysis of mitochondrial protein misfolding in Drosophila melanogaster". Cell Death & Differentiation. 19 (8): 1308–16. doi:10.1038/cdd.2012.5. PMC   3392634 . PMID   22301916.
  22. ↑ Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, González-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW (2004). "Hereditary early-onset Parkinson's disease caused by mutations in PINK1". Science. 304 (5674): 1158–60. Bibcode:2004Sci...304.1158V. doi: 10.1126/science.1096284 . PMID   15087508. S2CID   33630092.
  23. ↑ Hertz NT, Berthet A, Sos ML, Thorn KS, Burlingame AL, Nakamura K, Shokat KM (2013). "A neo-substrate that amplifies catalytic activity of parkinson's-disease-related kinase PINK1". Cell. 154 (4): 737–47. doi:10.1016/j.cell.2013.07.030. PMC   3950538 . PMID   23953109.
  24. ↑ Osgerby L, Lai YC, Thornton PJ, Amalfitano J, Le Duff CS, Jabeen I, Kadri H, Miccoli A, Tucker JH, Muqit M, Mehellou Y (2017). "Kinetin Riboside and Its ProTides Activate the Parkinson's Disease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independent of Mitochondrial Depolarization". J. Med. Chem. 60 (8): 3518–24. doi:10.1021/acs.jmedchem.6b01897. PMC   5410652 . PMID   28323427.
  25. ↑ Osgerby L, Lai YC, Thornton PJ, Amalfitano J, Le Duff CS, Jabeen I, Kadri H, Miccoli A, Tucker JH, Muqit M, Mehellou Y (2017). "Kinetin Riboside and Its ProTides Activate the Parkinson's Disease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independent of Mitochondrial Depolarization". J. Med. Chem. 60 (8): 3518–24. doi:10.1021/acs.jmedchem.6b01897. PMC   5410652 . PMID   28323427.
  26. ↑ Barini E, Miccoli A, Tinarelli F, Mulholand K, Kadri H, Khanim F, Stojanovski L, Read KD, Burness K, Blow JJ, Mehellou Y, Muqit M (2017). "The Anthelmintic Drug Niclosamide and its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1". ChemBioChem. 19 (5): 425–429. doi:10.1002/cbic.201700500. PMC   5901409 . PMID   29226533.

Further reading


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.