α-Synuclein-Induced Destabilized BMAL1 mRNA Leads to Circadian Rhythm Disruption in Parkinson's Disease

被引：6
作者：
Liu, Jun-Yi [1 ]
Xue, Jian [1 ,2 ]
Wang, Fen [2 ]
Wang, Ya-Li [3 ]
Dong, Wan-Li [1 ]
机构：
[1] Soochow Univ, Dushu Lake Hosp, Dept Neurol, Suzhou 214123, Peoples R China
[2] Soochow Univ, Inst Neurosci, Suzhou 215123, Peoples R China
[3] Nanjing Med Univ, Suzhou Municipal Hosp North, Dept Neurol, Suzhou 215008, Peoples R China
来源：
NEUROTOXICITY RESEARCH | 2023年 / 41卷 / 02期
基金：
中国国家自然科学基金;
关键词：
Circadian dysfunction; Parkinson's disease; alpha-Synuclein; BMAL1; CLOCK GENES; UBIQUITIN; HEALTH; BMAL1; BRAIN;
D O I：
10.1007/s12640-022-00633-0
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Circadian dysfunction is a common non-motor symptom in Parkinson's disease (PD). The potential influence of aggravated alpha-synuclein (SNCA) on circadian disruption remains unclear. SNCA(A53T)-overexpressing transgenic mice (SNCA(A53T) mice) and wild-type (WT) littermates were used in this study. The energy metabolism cage test showed differences in 24-h activity pattern between SNCA(A53T) and WT mice. When compared with the age-matched littermates, brain and muscle ARNT-like 1 (BMAL1) was downregulated in SNCA(A53T) mice. BMAL1 was downregulated in PC12 cells overexpressing SNCA. Degradation of BMAL1 protein remained unchanged after overexpression of SNCA, while its mRNA level decreased. miRNA (miR)-155 was upregulated by overexpression of SNCA, and downregulation of BMAL1 was partially reversed by transfection with miR-155 inhibitor. Our findings demonstrated that overexpression of SNCA induced biorhythm disruption and downregulated BMAL1 expression through decreasing stability of BMAL1 mRNA via miR-155.
引用
收藏
页码：177 / 186
页数：10
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