Contributions of circadian clock genes to cell survival in fibroblast models of lithium-responsive bipolar disorder

Differential contributions of circadian clock genes to cell survival in bipolar disorder patient derived neuronal progenitor cells distinguishes lithium responders and non-responders

“…In cellular models using patient fibroblasts or induced pluripotent stem cell (iPSC)-derived neurons, we have shown that circadian disruption is associated with non-response to lithium [ 14 , 16 ]. Linking to other research on neuronal loss in BD, our recent work in human fibroblasts has extended this finding to implicate overlap between circadian clocks and apoptosis pathways as potentially important [ 33 ]. These studies revealed differences in apoptosis and cellular protection from lithium in BD patient cells compared to controls, that molecular pathways regulating circadian rhythms and apoptosis overlap and that gene expression underlying circadian-apoptosis networks were distinctly organized in healthy controls, and in BD patients, with additional differences between lithium responders (Li-R) and non-responders (Li-NR).…”

“…Our previous work revealed that BD and control fibroblasts differ in the anti-apoptosis effects of lithium, but that the pro-survival benefit of lithium did not distinguish Li-R and Li-NR [ 33 ]. Our current study also found that there is no major difference in the cell death response to STS, or protective response to lithium that distinguishes Li-R and Li-NR.…”

“…through mediators such as P53. In our previous fibroblasts study, we found significant correlation of PER1 expression with the cell survival gene TP53 in control cells that was disrupted in BD [ 33 ]. Previous studies have documents functional interactions between PER1 and P53 proteins [ 40 ], and in studies of BD patients combining brain imaging and gene expression suggest that TP53 may contribute to the neuroprotective effects of lithium [ 41 ].…”

The association between ferroptosis and autophagy in cardiovascular diseases

“…77 Studies have shown that the disorder of circadian rhythm signaling pathway may lead to apoptosis, short-term circadian rhythm disorder may cause short-term discomfort, and longterm circadian rhythm disorder will lead to dysfunction of the body, thus causing disease. 78 Aryl hydrocarbon receptor nuclear translocator-like (ARNTL) is a circadian transcription factor that regulates the expression of downstream circadian genes by binding to the E-box gene regulatory elements in the promoter. 79 SQSTM1 is the cargo receptor required for clockophagy, under the action of SQSTM1, ARNTL can be selectively degraded.…”

“…Different organs and tissues have their own unique rhythms, which are interwoven together to co‐ordinate the steady state of the body 77 . Studies have shown that the disorder of circadian rhythm signaling pathway may lead to apoptosis, short‐term circadian rhythm disorder may cause short‐term discomfort, and long‐term circadian rhythm disorder will lead to dysfunction of the body, thus causing disease 78 . Aryl hydrocarbon receptor nuclear translocator‐like (ARNTL) is a circadian transcription factor that regulates the expression of downstream circadian genes by binding to the E‐box gene regulatory elements in the promoter 79 .…”