Circadian Rhythm Disruption and Alzheimer’s Disease: The Dynamics of a Vicious Cycle

Abstract

: All mammalian cells exhibit circadian rhythm in cellular metabolism and energetics. Autonomous cellular clocks are modulated by various pathways that are essential for robust time keeping. In addition to the canonical transcriptional translational feedback loop, several new pathways of circadian timekeeping - non-transcriptional oscillations, post-translational modifications, epigenetics and cellular signaling in the circadian clock - have been identified. The physiology of circadian rhythm is expansive, and its link to the neurodegeneration is multifactorial. Circadian rhythm disruption is prevelant in contamporary society where light-noise, shift-work, and transmeridian travel are commonplace, and is also reported from the early stages of Alzheimer's disease (AD). Circadian alignment by bright light therapy in conjunction with chronobiotics is beneficial for treating sundowning syndrome and other cognitive symptoms in advanced AD patients. We performed a comprehensive analysis of the clinical and translational reports to review the physiology of the circadian clock, delineate its dysfunction in AD, and unravel the dynamics of the vicious cycle between two pathologies. The review delineates the role of putative targets like clock proteins PER, CLOCK, BMAL1, ROR, and clock-controlled proteins like AVP, SIRT1, FOXO, and PK2 towards future approaches for management of AD. Furthermore, the role of circadian rhythm disruption in aging is delineated.

Comorbidity between Alzheimer’s disease and major depression: a behavioural and transcriptomic characterization study in mice

“…6b). In this sense, our results support previous research studies that examined the presence of circadian dysfunction in AD [97,98] and MD [99,100]. We observe the downregulation of Ciart and Dbp in the amygdala, striatum and PFC at 3 and 6 months old (Fig.…”

Adolescent Development of Biological Rhythms: Estradiol Dependence and Effects of Combined Contraceptives

“…Perturbation of body temperature rhythms is associated with diverse health insults across species, both reflecting perturbation in underlying systems and potentially acting as a causative agent. Circadian disruption to CBT rhythms occurs in, and is proportional to, severity of jetlag(158), depression(159), sepsis severity(160, 161), post-traumatic injury(162), cognitive decline(163), and has even been proposed as a root cause of disease dubbed “Circadian Syndrome”(164) . Disruption to ovulatory temperature rhythms occurs in anovulatory and atypical luteal phase cycles(165–167), including those arising from polycystic ovarian syndrome (PCOS)(168).…”

Embelin: A novel XIAP inhibitor for the prevention and treatment of chronic diseases

“…Some of the most common neurological disorders are Alzheimer's disease, Parkinson's disease, stroke, and multiple sclerosis, mostly caused by the loss of neurons and glial cells. [231][232][233][234] Embelin has been claimed as a potential candidate for the treatment of neurological disorders due to its remarkable pharmacological profile in pre-clinical studies. Several groups have claimed embelin as a potential multi-targeted anti-Alzheimer's agent.…”