alpha-synuclein and Hyperlipoproteinemia-Type-I

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.

Topics: alpha-Synuclein; Animals; Brain; Cell Nucleus; Cells, Cultured; Cytoplasm; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases; HEK293 Cells; Humans; Hyperlipoproteinemia Type I; Lipoprotein Lipase; Mice, Inbred C57BL; Mice, Knockout; Synaptosomes; Transfection; Ubiquitin Thiolesterase; Ubiquitination