Methamphetamine increases Prion Protein and induces dopamine-dependent expression of protease resistant PrPsc.

Methamphetamine increases Prion Protein and induces dopamine-dependent expression of protease resistant PrPsc. Arch Ital Biol. 2017 Jul 01;155(1-2):83-99 Authors: Ferrucci M, Ryskalin L, Biagioni F, Gambardella S, Busceti CL, Falleni A, Lazzeri G, Fornai F Abstract The cellular prion protein (PrPc) is physiologically expressed within selective brain areas of mammals. Alterations in the secondary structure of this protein lead to scrapie-like prion protein (PrPsc), which precipitates in the cell. PrPsc has been detected in infectious, inherited or sporadic neurodegenerative disorders. Prion protein metabolism is dependent on autophagy and ubiquitin proteasome. Despite not being fully elucidated, the physiological role of prion protein relates to chaperones which rescue cells under stressful conditions.Methamphetamine (METH) is a widely abused drug which produces oxidative stress in various brain areas causing mitochondrial alterations and protein misfolding. These effects produce a compensatory increase of chaperones while clogging cell clearing pathways. In the present study, we explored whether METH administration modifies the amount of PrPc. Since high levels of PrPc when the clearing systems are clogged may lead to its misfolding into PrPsc, we further tested whether METH exposure triggers the appearance of PrPsc. We analysed the effects of METH and dopamine administration in PC12 and striatal cells by using SDS-PAGE Coomassie blu...
Source: Archives Italiennes de Biologie - Category: Neuroscience Tags: Arch Ital Biol Source Type: research