Molecular mechanisms of neurodegeneration through the altered circadian clock

Circadian clock, a cell-autonomous oscillator, presents in most of the cells to drive a 24-h cycle in biological and behavioral processes. The core clock mechanism is composed of a transcriptional negative feedback loop, where the transcription factor BMAL1/CLOCK drives the expression of their target genes including their own inhibitors, Period (PER) and Cryptochrome (Cry), as well as other circadian output genes. As several lines of epidemiological evidence has indicated a bidirectional linkage between altered circadian rhythms and neurodegeneration, we take effort in exploring the underlying mechanisms in this association. In this study, we found that circadian clocks were altered in the presence of neurotoxic stimuli via a decline activity of transcription factors BMAL1-CLOCK in primary neurons. In addition, focal adhesion pathway and intracellular tension signaling relating to cytoskeleton were identified as the affected processes by neurodegeneration through RNA sequencing analysis. Taken together, our works aims to provide a comprehensive insight into a relationship between circadian clock and neurodegeneration.