Alteration of dynein function affects α-synuclein degradation via the autophagosome-lysosome pathway

International Journal of Molecular Sciences
Da LiChun-Feng Liu

Abstract

Growing evidence suggests that dynein dysfunction may be implicated in the pathogenesis of neurodegeneration. It plays a central role in aggresome formation, the delivery of autophagosome to lysosome for fusion and degradation, which is a pro-survival mechanism essential for the bulk degradation of misfolded proteins and damaged organells. Previous studies reported that dynein dysfuntion was associated with aberrant aggregation of α-synuclein, which is a major component of inclusion bodies in Parkinson's disease (PD). However, it remains unclear what roles dynein plays in α-synuclein degradation. Our study demonstrated a decrease of dynein expression in neurotoxin-induced PD models in vitro and in vivo, accompanied by an increase of α-synuclein protein level. Dynein down-regulation induced by siRNA resulted in a prolonged half-life of α-synuclein and its over-accumulation in A53T overexpressing PC12 cells. Dynein knockdown also prompted the increase of microtubule-associated protein 1 light chain 3 (LC3-II) and sequestosome 1 (SQSTM1, p62) expression, and the accumulation of autophagic vacuoles. Moreover, dynein suppression impaired the autophagosome fusion with lysosome. In summary, our findings indicate that dynein is critica...Continue Reading

References

Jan 1, 1997·ILAR Journal·J. Derrell ClarkDennis F. Kohn
Jun 28, 2005·Nature Genetics·Brinda RavikumarDavid C Rubinsztein
Dec 13, 2006·The European Journal of Neuroscience·He-Jin LeeSeung-Jae Lee
Feb 9, 2007·Proceedings of the National Academy of Sciences of the United States of America·G MorfiniS T Brady
Feb 10, 2007·The Journal of Biological Chemistry·Kevin W-H LoK Kevin Pfister
Mar 17, 2007·Lancet Neurology·Marta Martinez-Vicente, Ana Maria Cuervo
Mar 31, 2007·Nature Reviews. Drug Discovery·David C RubinszteinDaniel J Klionsky
Sep 12, 2007·The Journal of Cell Biology·James A OlzmannLih-Shen Chin
Jan 12, 2008·Brain : a Journal of Neurology·Tianhong PanJoseph Jankovic
Apr 5, 2008·Cell Structure and Function·Shunsuke KimuraTamotsu Yoshimori
Jan 13, 2009·Nature Genetics·Matthew J FarrerZbigniew K Wszolek
Mar 20, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Chee Yeun ChungOle Isacson
Aug 25, 2009·Experimental Neurology·Ida Rishal, Mike Fainzilber
Mar 5, 2010·The Journal of Biological Chemistry·Sally K MakDonato A Di Monte
Dec 21, 2010·Molecular Biology of the Cell·Serena C TanRichard B Vallee
Mar 23, 2011·Pharmacology & Therapeutics·Judith Eschbach, Luc Dupuis
Sep 23, 2011·Biochemical Society Transactions·Victoria J Allan
Feb 15, 2012·The Journal of Cell Biology·Sandra MadayErika L F Holzbaur
Jun 22, 2012·Brain : a Journal of Neurology·Yaping ChuJeffrey H Kordower
Sep 1, 2012·Molecular Neurobiology·Toru YasudaHideki Mochizuki
Apr 26, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Sibylle E Eisbach, Tiago F Outeiro

❮ Previous
Next ❯

Citations

Apr 27, 2016·PloS One·Raquel Muñoz-MorenoCovadonga Alonso
Sep 15, 2018·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Chang ShenToru Iwaki
Jul 19, 2016·Oncotarget·Srinivas AyyadevaraRobert J Shmookler Reis

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
transmission electron microscopy
PCR

Software Mentioned

SPSS
Image J

Related Concepts

Related Feeds

Alpha-Synuclein Aggregation

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.

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.