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

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.

Automated summary

Circadian dysfunction is a common non-motor symptom in Parkinson's disease. The potential influence of SNCA on circadian disruption remains unclear. This study showed that overexpression of SNCA induced biorhythm disruption and downregulated BMAL1 expression through decreasing stability of BMAL1 mRNA via miR-155.