Alteration of Upstream Autophagy-Related Proteins (ULK1, ULK2, Beclin1, VPS34 and AMBRA1) in Lewy Body Disease

被引：48

作者：

Miki, Yasuo ^{[1
]}

Tanji, Kunikazu ^{[1
]}

Mori, Fumiaki ^{[1
]}

Utsumi, Jun ^{[2
]}

Sasaki, Hidenao ^{[2
]}

Kakita, Akiyoshi ^{[3
]}

Takahashi, Hitoshi ^{[4
]}

Wakabayashi, Koichi ^{[1
]}

机构：

[1] Hirosaki Univ, Grad Sch Med, Inst Brain Sci, Dept Neuropathol, 5 Zaifu Cho, Hirosaki, Aomori 0368562, Japan

[2] Hokkaido Univ, Grad Sch Med, Dept Neurol, Sapporo, Hokkaido, Japan

[3] Niigata Univ, Dept Pathol Neurosci, Ctr Bioresource Based Res, Niigata, Japan

[4] Niigata Univ, Brain Res Inst, Dept Pathol, Niigata, Japan

来源：

BRAIN PATHOLOGY | 2016年 / 26卷 / 03期

关键词：

autophagy; dementia with Lewy bodies; Lewy body; Lewy body disease; Parkinson's disease; ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; REGULATE AUTOPHAGY; BRAIN; MACROAUTOPHAGY; DEMENTIA; RUBICON; LC3; PHOSPHORYLATION; ACCUMULATION;

D O I：

10.1111/bpa.12297

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

Autophagy is associated with the pathogenesis of Lewy body disease, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). It is known that several downstream autophagosomal proteins are incorporated into Lewy bodies (LBs). We performed immunostaining and Western blot analysis using a cellular model of PD and human brain samples to investigate the involvement of upstream autophagosomal proteins (ULK1, ULK2, Beclin1, VPS34 and AMBRA1), which initiate autophagy and form autophagosomes. Time course analysis of cultured cells transfected with flag-alpha-synuclein and synphilin-1 revealed upregulation of these upstream proteins with accumulation of LB-like inclusions. In human specimens, only mature LBs were positive for upstream autophagosomal proteins. Western blotting of fractionated brain lysates showed that upstream autophagosomal proteins were detected in the soluble and insoluble fraction in DLB, corresponding to the bands of phosphorylated alpha-synuclein. However, Western blot analysis of total brain lysates in PD and DLB showed that the increase of upstream autophagosomal proteins was only partial. The quantitative, qualitative and locational alteration of upstream autophagosomal proteins in the present study indicates their involvement in the pathogenesis of LB disease. Our data also suggest that misinduction or impairment of upstream autophagy might occur in the disease process of LB disease.

引用

页码：359 / 370

页数：12

共 61 条

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