Mitochondrial Dysfunction in Parkinson's Disease: New Mechanistic Insights and Therapeutic Perspectives.
TLDR
Increasing evidence supports the critical role for mitochondrial dysfunction in the development of sporadic PD, while the involvement of familial PD-related genes in the regulation of mitochondrial biology has been expanded by the discovery of new mitochondria-associated disease loci and the identification of their novel functions.Abstract:
Parkinson’s disease (PD) is a complex neurodegenerative disorder, the aetiology of which is still largely unknown. Overwhelming evidence indicates that mitochondrial dysfunction is a central factor in PD pathophysiology. Here we review recent developments around mitochondrial dysfunction in familial and sporadic PD, with a brief overview of emerging therapies targeting mitochondrial dysfunction. Increasing evidence supports the critical role for mitochondrial dysfunction in the development of sporadic PD, while the involvement of familial PD-related genes in the regulation of mitochondrial biology has been expanded by the discovery of new mitochondria-associated disease loci and the identification of their novel functions. Recent research has expanded knowledge on the mechanistic details underlying mitochondrial dysfunction in PD, with the discovery of new therapeutic targets providing invaluable insights into the essential role of mitochondria in PD pathogenesis and unique opportunities for drug development.read more
Citations
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References
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Tohru Kitada,Shuichi Asakawa,Nobutaka Hattori,Hiroto Matsumine,Yasuhiro Yamamura,Shinsei Minoshima,Masayuki Yokochi,Yoshikuni Mizuno,Nobuyoshi Shimizu +8 more
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Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
Eriza Maria Valente,Patrick M. Abou-Sleiman,Viviana Caputo,Miratul M. K. Muqit,Kirsten Harvey,Suzana Gispert,Zeeshan Ali,Domenico Del Turco,Anna Rita Bentivoglio,Daniel G. Healy,Alberto Albanese,Robert L. Nussbaum,Rafael González-Maldonado,Thomas Deller,S Salvi,Pietro Cortelli,William P. Gilks,David S. Latchman,Roberk J. Harvey,Bruno Dallapiccola,Georg Auburger,Nicholas W. Wood +21 more
TL;DR: The identification of two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6 families provide a direct molecular link between mitochondria and the pathogenesis of PD.
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PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
Sven Geisler,Kira M. Holmström,Diana Skujat,Fabienne C. Fiesel,Oliver Rothfuss,Philipp J. Kahle,Wolfdieter Springer +6 more
TL;DR: Functional links between PINK1, Parkin and the selective autophagy of mitochondria, which is implicated in the pathogenesis of Parkinson's disease, are provided.
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The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy
Michael Lazarou,Danielle A. Sliter,Lesley A. Kane,Shireen A. Sarraf,Chunxin Wang,Jonathon L. Burman,Dionisia P. Sideris,Adam I. Fogel,Richard J. Youle +8 more
TL;DR: Using genome editing to knockout five autophagy receptors in HeLa cells, this work shows that two receptors previously linked to xenophagy, NDP52 and optineurin, are the primary receptors for PINK1- and parkin-mediated mitophagy.