Epigenetic events influencing the biological clock: Panacea for neurodegeneration

Abstract

The human biological clock is the 24-h internal molecular network of circadian genes in synchronization with other cells in response to external stimuli. The rhythmicity of the clock genes is maintained by positive and negative transcriptional feedback loops coordinating the 24-h oscillation in different tissues. The superchiasmatic nucleus, the central pacemaker of the biological clock diminishes with aging causing alterations in the clock rhythmicity leading to the onset of neurodegenerative diseases mainly Alzheimer's disease, Parkinson's disease, and Huntington's disease. Studies have shown that brain and muscle Arnt -like 1 (Bmal1) and Circadian Locomotor Output Cycles Kaput (Clock) gene expression is altered in the onset of neurodegeneration. One of the major symptoms of neurodegeneration is changes in the sleep/wake cycle. Moreover, variations in circadian clock oscillations can happen due to lifestyle changes, addiction to alcohol, cocaine, drugs, smoking, food habits and most importantly eating and sleep/awake cycle patterns which can significantly impact the expression of circadian genes. Recent studies have focused on the molecular function of clock genes affected due to environmental cues. Epigenetic modifications are influenced by the external environmental factors. This review aims to focus on the principal mechanism of epigenetics influencing circadian rhythm disruption leading to neurodegeneration and as well as targeting the epigenetic modulators could be a novel therapeutic approach to combat neurodegenerative disorders.

Keywords

• Circadian
• Epigenetic regulation
• Phagocytosis
• Histone acetylation
• Inflammatory mediators
• Neurodegeneration