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Macroautophagy in sporadic and the genetic form of Parkinson’s disease with the A53T asynuclein mutation

Translational Neurodegeneration 2012年第1期1卷 4-10页

作者： Yue Huang Fariba Chegini germaine chua Karen Murphy Weiping Gai Glenda M Halliday Neuroscience Research Australia and the University of New South Wales Sydney2031Australia Department of Human Physiology and the Centre for Neuroscience Flinders University School of MedicineBedford ParkSA5042Australia

Background:The A53T mutation in the a-synuclein gene causes autosomal-dominant Lewy body Parkinson’s disease(PD).Cultured cell models have linked this mutation to increased cell macroautophagy,although evidence of enhanced macroautophagy in patients with this mutation has not been ***:To determine whether macroautophagy is increased by the A53T a-synuclein gene mutation in PD patients and cell ***:Formalin-fixed paraffin-embedded 10μm-thick tissue sections from the substantia nigra and anterior cingulate cortex of two PD patients with the A53T a-synuclein gene mutation were compared with four sporadic PD cases and four controls obtained from the Sydney Brain *** bodies were isolated from frontal cortex of a case with late stage PD(recruited from South Australian Brain Bank).Immunohistochemistry was performed for a-synuclein and the macroautophagy markers autophagy-specific gene(ATG)5,ATG6/Beclin1 and ATG8/***5Y cells were transfected with wild type or A53T mutant a-synuclein plasmids and observable changes in macroautophagy marker protein levels assessed using Western ***:a-Synuclein immunoreactive neurites and dots were more numerous in patients with A53T mutations compared with late stage sporadic PD patients,and perinuclear cytoplasmic a-synuclein aggregates were observed in the a-synuclein A53T gene transfected SH-SY5Y cells compared to wild type *** PD patients(with or without A53T mutations)had increased immunohistochemical evidence for macroautophagy compared with controls,and the levels of the ATG5 complex were equally increased in wild type and A53T a-synuclein gene transfected cells compared to ***:Despite increased a-synuclein accumulation with A53T mutations,macroautophagy is not increased above that observed in sporadic patients with PD or in cells transfected with wild type a-synuclein,suggesting that mutated a-synuclein protein is not removed by macroautophagy.

关键词： α-synuclein macroautophagy Parkinson’s disease

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