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Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains
Published on: January 5, 2016
Lipoprotein lipase deficiency leads to α-synuclein aggregation and ubiquitin C-terminal hydrolase L1 reduction
1Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China.
Abstract:
We have previously reported that presynaptic dysfunction and cognitive decline have been found in lipoprotein lipase (LPL) deficient mice, but the mechanism remains to be elucidated. Accumulating evidence supported that α-synuclein (α-syn) and ubiquitin C-terminal hydrolase L1 (UCHL1) are required for normal synaptic and cognitive function. In this study, we found that α-syn aggregated and the expression of UCHL1 decreased in the brain of LPL deficient mice. Reduction of UCHL1 was resulted from nuclear retention of DNA cytosine-5-methyltransferase 1 in LPL knockout mice. Reverse changes were found in cultured cells overexpressing LPL. Furthermore, deficiency of LPL increased ubiquitination of α-syn. These results indicated that aggregation of α-syn and reduction of UCHL1 expression in LPL-deficient mice may affect synaptic function.
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