Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy

Science
Ana Maria CuervoDavid Sulzer

Abstract

Aberrant alpha-synuclein degradation is implicated in Parkinson's disease pathogenesis because the protein accumulates in the Lewy inclusion bodies associated with the disease. Little is known, however, about the pathways by which wild-type alpha-synuclein is normally degraded. We found that wild-type alpha-synuclein was selectively translocated into lysosomes for degradation by the chaperone-mediated autophagy pathway. The pathogenic A53T and A30P alpha-synuclein mutants bound to the receptor for this pathway on the lysosomal membrane, but appeared to act as uptake blockers, inhibiting both their own degradation and that of other substrates. These findings may underlie the toxic gain-of-function by the mutants.

References

Aug 1, 1990·Trends in Biochemical Sciences·J F Dice
Jan 1, 1997·Human Molecular Genetics·R L Nussbaum, M H Polymeropoulos
Nov 24, 1999·The Journal of Biological Chemistry·M C BennettM M Mouradian
Feb 17, 2001·Current Opinion in Structural Biology·V GrantcharovaA L Horwich
Aug 3, 2001·Nature Reviews. Neuroscience·K S McNaughtP Jenner
Mar 28, 2002·Physiological Reviews·Michael H Glickman, Aaron Ciechanover
Oct 29, 2002·Molecular and Cellular Neurosciences·Hardy J Rideout, Leonidas Stefanis
Apr 30, 2003·The Journal of Biological Chemistry·Julie L WebbDavid C Rubinsztein
Sep 16, 2003·Neuron·William Dauer, Serge Przedborski
Feb 27, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·He-Jin LeeSeung-Jae Lee
Apr 23, 2004·Trends in Cell Biology·Ana Maria Cuervo
May 5, 2004·The Journal of Cell Biology·Christina A WilsonVirginia M-Y Lee

❮ Previous
Next ❯

Citations

Apr 17, 2013·JAMA Neurology·Michael A NallsEllen Sidransky
Nov 8, 2012·Cellular and Molecular Life Sciences : CMLS·Dong WangP Robin Hiesinger
Sep 15, 2010·Acta Neuropathologica·Ozlem Goker-AlpanEllen Sidransky
Jun 30, 2012·Acta Neuropathologica·Darius Ebrahimi-FakhariPamela J McLean
Jan 15, 2013·Acta Neuropathologica·Nivetha RamachandranBerge A Minassian
Dec 25, 2012·Acta Neuropathologica·Akiko FurutaKeiji Wada
Sep 20, 2008·Journal of Neurology·Saskia BiskupThomas Gasser
Apr 17, 2013·Journal of Neurology·Tom Foltynie, Joshua Kahan
Sep 24, 2010·Journal of Neural Transmission·Isidre FerrerMargarita Carmona
Apr 4, 2006·Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society·Otto AppenzellerYang Wang
Jan 24, 2009·Apoptosis : an International Journal on Programmed Cell Death·Oren A LevyLloyd A Greene
Feb 5, 2010·Apoptosis : an International Journal on Programmed Cell Death·Hansruedi Büeler
Feb 19, 2010·Apoptosis : an International Journal on Programmed Cell Death·Qian Yang, Zixu Mao
Sep 12, 2006·Biogerontology·Mehmet Alper ArslanCsaba Soti
Apr 5, 2011·Biogerontology·Vanessa M HubbardAna Maria Cuervo
Jul 25, 2013·Biotechnology Letters·Yeon Jung KimGyun Min Lee
Apr 30, 2010·Journal of Inherited Metabolic Disease·Cinzia Maria Bellettato, Maurizio Scarpa
Oct 1, 2013·Cell Biology and Toxicology·Hui-Hsing HungChien-Yuan Pan
Sep 4, 2007·Current Neurology and Neuroscience Reports·Annamaria Ventruti, Ana Maria Cuervo
Apr 29, 2010·Current Neurology and Neuroscience Reports·Arash VelayatiEllen Sidransky
May 28, 2013·Cell Biochemistry and Biophysics·Caroline Park, Ana Maria Cuervo
Mar 7, 2009·Journal of Molecular Neuroscience : MN·Michael RiedelChristiane Richter-Landsberg
Mar 1, 2012·Journal of Molecular Neuroscience : MN·Xin YuAnna-Lena Ström
Dec 30, 2011·Molecular Neurobiology·Ilse S PienaarDavid Dexter
Jul 10, 2012·Molecular Neurobiology·Maria Teresa Viscomi, Marcello D'Amelio
Aug 18, 2012·Molecular Neurobiology·Elzbieta JandaVincenzo Mollace
Sep 1, 2012·Molecular Neurobiology·Toru YasudaHideki Mochizuki
Sep 4, 2012·Molecular Neurobiology·Maria XilouriLeonidas Stefanis
May 31, 2007·Journal of Biosciences·C Söti, Péter Csermely
Jun 16, 2009·Neurotoxicity Research·Irmgard ParisJuan Segura-Aguilar
May 12, 2005·Parkinsonism & Related Disorders·Serge Przedborski
Jun 29, 2007·Expert Reviews in Molecular Medicine·Jean-Christophe Rochet
Mar 23, 2011·Expert Reviews in Molecular Medicine·Maria Xilouri, Leonidas Stefanis
Mar 2, 2010·The Journal of Physical Chemistry. B·Farzin HaqueJennifer S Hovis
Feb 5, 2013·Acta Pharmacologica Sinica·Warren E HochfeldDavid C Rubinsztein
Apr 23, 2013·Acta Pharmacologica Sinica·Fang YangChun-feng Liu

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.

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