A Comprehensive Update on the Etiopathogenesis of Amyotrophic Lateral Sclerosis with Specific Emphasis on Gut Microbiota (GM), Enteric Nervous System (ENS) and Associated Crosstalk of Astrocytes, GM, Muscle with Mitochondrial Melatonergic Pathway-A Narrative Review

Kaur KK, Allahbadia GN and Singh M

Published on: 2023-08-20

Abstract

Earlier having reviewed the part of gut-Microbiota (GM) in obesity, Type 1 diabetes mellitus (T1D), NAFLD/NASH, Osteoarthritis, Kidney diseases, in Neuropsychiatric Diseases, Etiopathogenesis and intestinal flora importance in dysbiosis subsequent to ischemic stroke, we found practically every organ/tissue’s body pathology is correlated with altered GM. Further part of mitochondrial transport in Etiopathogenesis/management of various CNS neurodegenerative diseases review here we further decided to review Etiopathogenesis is of Amyotrophic Lateral sclerosis (ALS); a very frustrating disease to treat in clinical arena. ALS is a propagating neurodegenerative disease with involvement of motor neurons (MN) in the spinal cord, medulla oblongata along and cerebral cortex .The manifestation of maximum patients with the canonical ALS is basically atrophy, muscle weakness and fasciculations with survival of just 3-5 yrs. subsequent, to diagnosis. Thus a narrative review was carried out using various search engine with the MeSH terms; Amyotrophic Lateral sclerosis (ALS); upper MN (UMN) ;lower MN (LMN) demise; free radicals; glutamate excitotoxicity; oxidative stress; inflammation; Gut Microbiota (GM); T1D; Familial /Sporadic ALS; enteric nervous system (ENS); from 2000’still date in 2023where we selected 85 articles for this review. 2 kinds of ALS are i) Familial is totally secondary to genetic changes whereas sporadic kind is having multifactorial etiology initiation of ALS. Numerous events are implicated in the ALS pathophysiology inclusive of Oxidative stress (OS), glutamate excitotoxicity, neuroinflammation. Furthermore it is posited that risk factors which are responsible for conditioning like predisposition to neurodegeneration in motor neurons, degree of strenuous exercise, intestinal Dysbiosis, ENS implications that validate the current posits of disease generation; crosstalk amongst Astrocytes, Gut Micro biome, Muscle with in ALS through Mitochondrial Melatonergic pathway and disturbance by glyphosate based herbicides is needed to be explored for better life quality/survival. It is imperative to attain further greater insight for life quality/survival improvement.