Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases

• Published in: International journal of molecular sciences 2020-10, Vol.21 (19), p.7174
• Main Authors: Luo, Fang, Sandhu, Aaron F, Rungratanawanich, Wiramon, Williams, George E, Akbar, Mohammed, Zhou, Shuanhu, Song, Byoung-Joon, Wang, Xin
• Format: Article
• Language: English
• Subjects: Aging; Aging - genetics; Aging - metabolism; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer Disease - prevention & control; Alzheimer's disease; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - pathology; Amyotrophic Lateral Sclerosis - prevention & control; Animals; Antioxidants; Antioxidants - metabolism; Antioxidants - pharmacology; Apoptosis; Autophagy; Autophagy (Cytology); Autophagy - drug effects; Autophagy - genetics; Autophagy-Related Proteins - agonists; Autophagy-Related Proteins - genetics; Autophagy-Related Proteins - metabolism; Calcium channels; Cell death; Chemical compounds; Circadian Rhythm - physiology; Circadian rhythms; Cytoplasm; Degeneration; Endoplasmic reticulum; Etiology; Health aspects; Homeostasis; Humans; Huntington Disease - genetics; Huntington Disease - metabolism; Huntington Disease - pathology; Huntington Disease - prevention & control; Huntington's disease; Huntingtons disease; Kinases; Melatonin; Melatonin - biosynthesis; Melatonin - pharmacology; Membranes; Mitochondria; Nervous system; Nervous System - drug effects; Nervous System - metabolism; Nervous System - pathology; Neurodegeneration; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotection; Neuroprotective Agents - metabolism; Neuroprotective Agents - pharmacology; Organelles; Organophosphates; Oxidative stress; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson Disease - prevention & control; Parkinson's disease; Pathogenesis; Phagocytosis; Pharmacology; Physiology; Pineal gland; Pineal Gland - physiology; Proteins; Review
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21197174

With aging, the nervous system gradually undergoes degeneration. Increased oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and cell death are considered to be common pathophysiological mechanisms of various neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), organophosphate-induced delayed neuropathy (OPIDN), and amyotrophic lateral sclerosis (ALS). Autophagy is a cellular basic metabolic process that degrades the aggregated or misfolded proteins and abnormal organelles in cells. The abnormal regulation of neuronal autophagy is accompanied by the accumulation and deposition of irregular proteins, leading to changes in neuron homeostasis and neurodegeneration. Autophagy exhibits both a protective mechanism and a damage pathway related to programmed cell death. Because of its "double-edged sword", autophagy plays an important role in neurological damage and NDDs including AD, PD, HD, OPIDN, and ALS. Melatonin is a neuroendocrine hormone mainly synthesized in the pineal gland and exhibits a wide range of biological functions, such as sleep control, regulating circadian rhythm, immune enhancement, metabolism regulation, antioxidant, anti-aging, and anti-tumor effects. It can prevent cell death, reduce inflammation, block calcium channels, etc. In this review, we briefly discuss the neuroprotective role of melatonin against various NDDs via regulating autophagy, which could be a new field for future translational research and clinical studies to discover preventive or therapeutic agents for many NDDs.