The role of BMAL1 in glial cells: Implications for cognitive function in neurodegenerative diseases

Disruption of the circadian rhythm may precede the typical clinical symptoms of neurodegenerative diseases and is a potential risk factor for Alzheimer's disease (AD), associated dementias, and Parkinson's disease (PD). The morphology and function of mammalian glial cells and their gene expression correlate with circadian rhythms. Brain and muscle Arnt-like protein-1(BMAL1) is a core player in the functional regulation of glial cells and is a major regulator of circadian rhythms. According to new research, neuroglial BMAL1 is implicated in several pathological processes, including altered energy metabolism, dysregulated protein homeostasis, decreased synaptic plasticity, disrupted myelin formation and regeneration, and neuroinflammation, which are correlated with cognitive impairment in neurodegenerative diseases. To provide concepts and perspectives for precision medicine of the disease, we have systematically summarized the mechanism of action of neuroglial BMAL1 in cognitive impairment in neurodegenerative diseases and related studies, established a signaling network map between neuroglial BMAL1 and cognitive impairment, and discussed therapeutic strategies targeting neuroglial BMAL1.