机构：[a]Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China首都医科大学宣武医院神经生物学研究室[b]National Clinical Research Center for Geriatric Disorders, Beijing, China
Aging is associated with an increased risk for Parkinson's disease and dementia with Lewy bodies, in which alpha-synuclein (alpha-syn) oligomerization plays key pathogenic roles. Here, we show that oligomeric alpha-syn levels increase with age in the human brain and are accompanied by a decrease in the activity of glucocerebrosidase (GCase), a lysosomal enzyme whose dysfunction is linked to the accumulation of oligomeric alpha-syn. The inverse relationship between oligomeric alpha-syn levels and GCase activity was more evident in brain regions susceptible to neurodegeneration (i.e., the striatum and hippocampus) than those that are less vulnerable (i.e., the cerebellum and occipital cortex). GCase could potentially regulate a-syn oligomerization, as demonstrated by the decrease in oligomeric alpha-syn levels caused by a GCase agonist. In vitro experiments showed that GCase activity was more potently inhibited by oligomeric than monomeric alpha-syn in the lysosome-enriched fractions isolated from brain tissues and cultured neuronal cells. Alterations in oligomeric alpha-syns and their association with GCase in aging brains may explain the vulnerability of certain brain regions to neurodegeneration in Parkinson's disease and dementia with Lewy bodies.
基金：
Beijing Nova Program(Z181100006218052, xx2018096), the Natural Science Foundation of China (81671244, 81371200, and 81401042), the Beijing Municipal Science & Technology Commission (Z161100005116011,Z171100000117013), and the Beijing Municipal Commission of Healthand Family Planning (PXM2017_026283_000002).
第一作者机构：[a]Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China[b]National Clinical Research Center for Geriatric Disorders, Beijing, China[*1]Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital of China Capital Medical University, 45 Changchun Street,Beijing 100053, China.
通讯作者：
通讯机构：[*1]Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital of China Capital Medical University, 45 Changchun Street,Beijing 100053, China.
推荐引用方式(GB/T 7714)：
Weiwei Yang,Xuran Lia,Na Yin.Increased a-synuclein oligomerization is associated with decreased activity of glucocerebrosidase in the aging human striatum and hippocampus[J].NEUROSCIENCE LETTERS.2020,733:doi:10.1016/j.neulet.2020.135093.
APA：
Weiwei Yang,Xuran Lia&Na Yin.(2020).Increased a-synuclein oligomerization is associated with decreased activity of glucocerebrosidase in the aging human striatum and hippocampus.NEUROSCIENCE LETTERS,733,
MLA：
Weiwei Yang,et al."Increased a-synuclein oligomerization is associated with decreased activity of glucocerebrosidase in the aging human striatum and hippocampus".NEUROSCIENCE LETTERS 733.(2020)
