Title:Melatonin as a Harmonizing Factor of Circadian Rhythms, Neuronal Cell
Cycle and Neurogenesis: Additional Arguments for Its Therapeutic Use in
Alzheimer’s Disease
Volume: 21
Issue: 5
Author(s): Mayuri Shukla and Bruno Vincent*
Affiliation:
- Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand
- Institute of Molecular and
Cellular Pharmacology, Laboratory of Excellence DistALZ, Université Côte d'Azur, INSERM, CNRS, Sophia-Antipolis,
06560, Valbonne, France
Keywords:
Melatonin, circadian rhythm, cell cycle, Alzheimer’s disease, neurogenesis, therapeutic.
Abstract: The synthesis and release of melatonin in the brain harmonize various physiological functions.
The apparent decline in melatonin levels with advanced aging is an aperture to the neurodegenerative
processes. It has been indicated that down regulation of melatonin leads to alterations of circadian
rhythm components, which further causes a desynchronization of several genes and results in an
increased susceptibility to develop neurodegenerative diseases. Additionally, as circadian rhythms and
memory are intertwined, such rhythmic disturbances influence memory formation and recall. Besides,
cell cycle events exhibit a remarkable oscillatory system, which is downstream of the circadian phenomena.
The linkage between the molecular machinery of the cell cycle and complex fundamental
regulatory proteins emphasizes the conjectural regulatory role of cell cycle components in neurodegenerative
disorders such as Alzheimer’s disease. Among the mechanisms intervening long before
the signs of the disease appear, the disturbances of the circadian cycle, as well as the alteration of the
machinery of the cell cycle and impaired neurogenesis, must hold our interest. Therefore, in the present
review, we propose to discuss the underlying mechanisms of action of melatonin in regulating the
circadian rhythm, cell cycle components and adult neurogenesis in the context of AD pathogenesis
with the view that it might further assist to identify new therapeutic targets.