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

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.