期刊
BRAIN RESEARCH
卷 1681, 期 -, 页码 1-13出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2017.12.026
关键词
Synuclein; Dementia with Lewy bodies; Autophagy; Neurodegeneration
资金
- BRACE (Bristol Research into Alzheimer's and Care for Elderly)
- Northcott Devon Medical Foundation (UK)
- Plymouth University
- Alzheimer's Research UK
- Alzheimer's Society UK
- UK Medical Research Council
- UK Medical Research Council [G0400074]
- NIHR Newcastle Biomedical Research Centre
- MRC [G0400074] Funding Source: UKRI
- Medical Research Council [G0400074] Funding Source: researchfish
Dementia with Lewy bodies (DLB) is the second most prevalent neurodegenerative dementia, where an accumulation of aggregated fibrillar alpha-synuclein in neurons of limbic and forebrain regions of the brain leads to visual hallucination, cognitive impairment of a fluctuating nature and extrapyramidal motor disturbances. Beta-synuclein counteracts aggregation of alpha-synuclein in vitro and in animal models, however it is not clear whether this effect occurs in human Lewy body dementia (LBD) diseases. Here we examine expression of alpha-, beta-synuclein and autophagy markers in the frontal cortex (BA9) and occipital cortex (BA18-19) of patients with neuropathologically confirmed DLB/LBD and age-matched controls. We provide evidence for neuronal upregulation of beta-synuclein within the frontal cortex and its decrease in occipital cortex of DLB patients. While beta-synuclein-containing neurons were consistently devoid of oligomeric alpha-synuclein in the frontal cortex, we did not observe an overall correlation between total beta-synuclein and 5G4 levels (marker of oligomeric alpha-synuclein). The autophagy markers LC3-II and p62 were increased in the areas of beta-synuclein upregulation in DLB brains, and we show attenuation of autophagy flux when beta-synuclein is overexpressed in vitro. Altogether, this data suggests that beta-synuclein changes in DLB may exacerbate neuronal dysfunction caused by accumulation of alpha-synuclein by influencing protein degradation pathways: this should be taken into consideration when designing therapeutic strategies aimed to decrease alpha-synuclein burden in Lewy body diseases. (C) 2017 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据