Core Circadian Protein BMAL1: Implication for Nervous System Functioning and Its Diseases

The brain and muscle ARNT-like 1 protein, also known as BMAL1 or ARNTL1, is one of the key transcriptional regulators of circadian rhythms that controls the diurnal dynamics of a wide range of behavioral, hormonal, and biochemical factors in most living creatures around the Earth. This protein also regulates many physiological processes, and its disruption leads to pathological conditions in organisms, including nervous system disorders. The high evolutionary conservativity of BMAL1 allows for the construction of in vitro and in vivo models using experimental animals and the investigation of BMAL1-dependent molecular mechanisms of these diseases. In this review, we have collected data from human and animal studies concerning the roles of BMAL1 in processes such as neuroinflammation, trauma and neurodegeneration, neurodevelopment and myelinization, mood disorders, addictions, cognitive functions, and neurosignaling. Additionally, we provide information about the biochemical regulation of BMAL1 and pharmacological approaches to change its activity. Here, we conclude that BMAL1 functions in the nervous system go far beyond circadian rhythm regulation in most cell types, including neurons, glial cells, and microglial cells. Under pathological conditions, lack or overexpression of this protein can exert both protective and destructive effects. Thus, proper therapeutic modulation of BMAL1 activity is a promising approach for improving nervous system disorders.