Proteasome inhibition causes nigral degeneration with inclusion bodies in rats
作者： Kevin St. P. McNaught , Lars M. Bj??rklund , Roger Belizaire , Ole Isacson , Peter Jenner
DOI: 10.1097/00001756-200208070-00018
关键词:
摘要: Structural and functional defects in 26/20S proteasomes occur the substantia nigra pars compacta may underlie protein accumulation, Lewy body formation dopaminergic neuronal death Parkinson's disease. We therefore determined pathogenicity of proteasomal impairment following stereotaxic unilateral infusion lactacystin, a selective proteasome inhibitor, into rats. These animals became progressively bradykinetic, adopted stooped posture displayed contralateral head tilting. Administration apomorphine to lactacystin-treated rats reversed behavioral abnormalities induced rotations. Lactacystin caused dose-dependent degeneration cell bodies processes with cytoplasmic accumulation aggregation alpha-synuclein form inclusion bodies. findings support notion that failure ubiquitin-proteasome system degrade clear unwanted proteins is an important etiopathogenic factor
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