A Cleaning Crew: The Pursuit of Autophagy in Parkinson's Disease

ACS Chemical Neuroscience
Pathik ParekhAmit Khairnar

Abstract

Parkinson's disease (PD) is the second-most common neurodegenerative disorder, neuropathologically characterized by the aggregation of misfolded α-synuclein (α-syn) protein, which appears to be central to the onset and progression of PD pathology. Evidence from pioneering studies has highly advocated the existence of impaired autophagy pathways in the brains of PD patients. Autophagy is an evolutionarily conserved, homeostatic mechanism for minimizing abnormal protein aggregates and facilitating organelle turnover. Any aberration in constitutive autophagy activity results in the aggregation of misfolded α-syn, which, in turn, may further inhibit their own degradation-leading to a vicious cycle of neuronal death. Despite the plethora of available literature, there are still lacunas existing in our understanding of the exact cellular interplay between autophagy impairment and α-syn accumulation-mediated neurotoxicity. In this context, clearance of aggregated α-syn via up-regulation of the autophagy-lysosomal pathway could provide a pharmacologically viable approach to the treatment of PD. The present Review highlights the basics of autophagy and detrimental cross-talk between α-syn and chaperone-mediated autophagy, and α-syn and ...Continue Reading

References

Nov 1, 1967·The Journal of Cell Biology·R L DeterC De Duve
Aug 28, 1997·Nature·M G SpillantiniM Goedert
Sep 23, 2003·Movement Disorders : Official Journal of the Movement Disorder Society·Maria J MartíJaume Campdelacreu
Nov 1, 2003·Science·A B SingletonK Gwinn-Hardy
Sep 29, 2004·Lancet·Marie-Christine Chartier-HarlinAlain Destée
Sep 28, 2005·The Journal of Cell Biology·Sovan SarkarDavid C Rubinsztein
Feb 22, 2007·Annual Review of Nutrition·Noboru Mizushima, Daniel J Klionsky
Sep 1, 2007·Science·Jongpil KimAsa Abeliovich
Jan 4, 2008·The Journal of Clinical Investigation·Marta Martinez-VicenteAna Maria Cuervo
Jan 10, 2008·Journal of Neurochemistry·Edward D PloweyCharleen T Chu
Jan 15, 2008·Cell·Beth Levine, Guido Kroemer
Jun 21, 2008·The Journal of Biological Chemistry·Tereza VogiatziLeonidas Stefanis
Jun 24, 2008·Annals of Neurology·Owen A RossMatthew J Farrer
May 23, 2009·Journal of Cell Science·Brinda RavikumarDavid C Rubinsztein
Jul 15, 2009·Autophagy·Nao HosokawaNoboru Mizushima
Jul 23, 2009·Science Signaling·Emanuela SantiniGilberto Fisone
Oct 30, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Brian SpencerEliezer Masliah
Nov 10, 2009·Nature Cell Biology·Mitsuko Hayashi-NishinoAkitsugu Yamamoto
Jan 30, 2010·Parkinsonism & Related Disorders·Kristoffer Haugarvoll, Zbigniew K Wszolek
Mar 5, 2010·The Journal of Biological Chemistry·Sally K MakDonato A Di Monte
May 12, 2010·Proceedings of the National Academy of Sciences of the United States of America·Youren TongJie Shen
Aug 11, 2010·Archives of Neurology·Lydia Alvarez-ErvitiAnthony H V Schapira
Sep 22, 2010·The Journal of Cell Biology·Ashley R WinslowDavid C Rubinsztein
Feb 10, 2011·Neurobiology of Disease·Lydia Alvarez-ErvitiJ Mark Cooper
Jul 19, 2011·American Journal of Human Genetics·Alexander ZimprichTim M Strom
Oct 21, 2011·Human Molecular Genetics·Patricia Gómez-SuagaSabine Hilfiker
Feb 9, 2012·Cold Spring Harbor Perspectives in Medicine·Christine Klein, Ana Westenberger
Jun 1, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lauren G FriedmanZhenyu Yue
Aug 28, 2012·Molecular Neurodegeneration·Karin M DanzerPamela J McLean
Nov 16, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ishrat AhmedJoseph M Savitt
Jan 18, 2013·Parkinson's Disease·Todd J Swick
Mar 28, 2013·The Journal of Biological Chemistry·Selcuk A TanikVirginia M Y Lee

❮ Previous
Next ❯

Citations

Jun 5, 2021·Frontiers in Molecular Biosciences·Attila LehotzkyJudit Ovádi
Jul 3, 2021·Molecular Neurobiology·Tarapati RanaSimona Bungau

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Parkinson's Disease & Autophagy (MDS)

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Parkinson's Disease & Autophagy

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.