Importance of Bmal1 in Alzheimer's disease and associated aging‐related diseases: Mechanisms and interventions

Abstract With the aging world population, the prevalence of aging‐related disorders is on the rise. Diseases such as Alzheimer's, type 2 diabetes mellitus (T2DM), Parkinson's, atherosclerosis, hypertension, and osteoarthritis are age‐related, and most of these diseases are comorbidities or risk factors for AD; however, our understandings of molecular events that regulate the occurrence of these diseases are still not fully understood. Brain and muscle Arnt‐like protein‐1 (Bmal1) is an irreplaceable clock gene that governs multiple important physiological processes. Continuous research of Bmal1 in AD and associated aging‐related diseases is ongoing, and this review picks relevant studies on a detailed account of its role and mechanisms in these diseases. Oxidative stress and inflammation turned out to be common mechanisms by which Bmal1 deficiency promotes AD and associated aging‐related diseases, and other Bmal1‐dependent mechanisms remain to be identified. Promising therapeutic strategies involved in the regulation of Bmal1 are provided, including melatonin, natural compounds, metformin, d‐Ser2‐oxyntomodulin, and other interventions, such as exercise, time‐restricted feeding, and adiponectin. The establishment of the signaling pathway network for Bmal1 in aging‐related diseases will lead to advances in the comprehension of the molecular and cellular mechanisms, shedding light on novel treatments for aging‐related diseases and promoting aging‐associated brain health.