alpha-synuclein and Fever

The present study aimed to examine the proteins involved in the methamphetamine (MA)-induced nigrostriatal dopaminergic toxicity. Infusion of anisomycin into striatum and substantia nigra both abolished the MA-induced striatal dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) depletions, indicating a critical role of local protein synthesis in determining such dopaminergic toxicity. Moreover, local protein synthesis blockade reversed this neurotoxicity via a temperature-independent mechanism. We then employed a proteomic approach, two-dimensional gel electrophoresis (2-DE) in conjunction with mass spectrometry analysis, to identify the protein candidates associated with the MA-induced neurotoxicity. In striatal samples, 2-DE analysis revealed that the intensities of nine protein spots were altered by MA treatment. Mass spectrometry analysis allowed us to identify five proteins, including an up-regulated protein, alpha-synuclein, and four down-regulated proteins, ATPase, F-actin capping protein beta subunit, ubiquitin carboxy-terminal hydrolase/PGP 9.5, and peroxidase. MA-altered expression levels of alpha-synuclein and ubiquitin carboxy-terminal hydrolase/PGP 9.5 in striata were confirmed by western blotting analysis. Taken together, these results suggest that local up-regulation of alpha-synuclein and down-regulation of ubiquitin carboxy-terminal hydrolase/PGP 9.5 could be linked to the MA-induced dopaminergic terminal toxicity.

Topics: 3,4-Dihydroxyphenylacetic Acid; alpha-Synuclein; Animals; Anisomycin; Blotting, Western; Corpus Striatum; Dopamine; Electrophoresis, Gel, Two-Dimensional; Fever; Male; Mass Spectrometry; Methamphetamine; Mice; Mice, Inbred Strains; Nerve Tissue Proteins; Neurotoxins; Protein Synthesis Inhibitors; Substantia Nigra; Synucleins; Ubiquitin; Ubiquitin Thiolesterase