Title:Circadian Rhythm Disruption and Alzheimer’s Disease: The Dynamics of a Vicious Cycle
Volume: 19
Issue: 2
Author(s): Ashish Sharma*, Gautam Sethi, Murtaza M. Tambuwala, Alaa A. A. Aljabali, Dinesh Kumar Chellappan, Kamal Dua and Rohit Goyal*
Affiliation:
- Neuropharmacology Laboratory, School of Pharmaceutical Sciences, Shoolini University, Solan 173 212, Himachal Pradesh,India
- Neuropharmacology Laboratory, School of Pharmaceutical Sciences, Shoolini University, Solan 173 212, Himachal Pradesh,India
Keywords:
Circadian rhythm coupling, redox, suprachiasmatic nuclei, sleep-wake cycle, post-translational modifications,
aging.
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.
