期刊
NEUROSCIENCE LETTERS
卷 678, 期 -, 页码 118-123出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2018.05.009
关键词
Alpha-Synuclein; Autophagy; MicroRNA-7; Parkinson disease
资金
- National Institute of Health [NS70898, NS095003]
Alpha-Synuclein (alpha-Syn) is an important protein in the pathogenesis of Parkinson disease (PD) as it accumulates as fibrillar inclusions in affected brain regions including dopaminergic neurons in the substantia nigra. Elevated levels of alpha-Syn seem to be crucial in mediating its toxicity. Thus, detailed information regarding the regulatory mechanism of alpha-Syn expression in several layers such as transcription, post-transcription and post-translation is needed in order to devise therapeutic interventions for PD. Previously, we reported that expression of alpha-Syn is repressed by microRNA-7 (miR-7) through its effect on the 3'-untranslated region (UTR) of alpha-Syn mRNA. Here, we show that miR-7 also accelerates the clearance of alpha-Syn and its aggregates by promoting autophagy in differentiated ReNcell VM cells. Further, miR-7 facilitates the degradation of pre-formed fibrils of alpha-Syn transported from outside the cells. This additional mechanism for reducing alpha-Syn levels show miR-7 to be an important molecular target for PD and other alpha-synucleinopathies.
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