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Alteration of Dynein Function Affects ɑ-Synuclein Degradation via the Autophagosome-Lysosome Pathway.
- Source :
-
International Journal of Molecular Sciences . Dec2013, Vol. 14 Issue 12, p24242-24254. 13p. 4 Graphs. - Publication Year :
- 2013
-
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 ɑ-synuclein, which is a major component of inclusion bodies in Parkinson's disease (PD). However, it remains unclear what roles dynein plays in ɑ-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 ɑ-synuclein protein level. Dynein down-regulation induced by siRNA resulted in a prolonged half-life of ɑ-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 critical for the clearance of aberrant ɑ-synuclein via autophagosome-lysosome pathway. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DYNEIN
*SYNUCLEINS
*AUTOPHAGY
*LYSOSOMES
*BRAIN diseases
Subjects
Details
- Language :
- English
- ISSN :
- 16616596
- Volume :
- 14
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 93319507
- Full Text :
- https://doi.org/10.3390/ijms141224242