Neuromuscular Junction Dysfunction in Amyotrophic Lateral Sclerosis

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2022 Jan 8

PMID 34997540

Citations 40

Authors

Sagar Verma

Shiffali Khurana

Abhishek Vats

Bandana Sahu

Nirmal Kumar Ganguly

Pradip Chakraborti

Mandaville Gourie-Devi

Vibha Taneja

Affiliations

Soon will be listed here.

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive degeneration of motor neurons leading to skeletal muscle denervation. Earlier studies have shown that motor neuron degeneration begins in motor cortex and descends to the neuromuscular junction (NMJ) in a dying forward fashion. However, accumulating evidences support that ALS is a distal axonopathy where early pathological changes occur at the NMJ, prior to onset of clinical symptoms and propagates towards the motor neuron cell body supporting "dying back" hypothesis. Despite several evidences, series of events triggering NMJ disassembly in ALS are still obscure. Neuromuscular junction is a specialized tripartite chemical synapse which involves a well-coordinated communication among the presynaptic motor neuron, postsynaptic skeletal muscle, and terminal Schwann cells. This review provides comprehensive insight into the role of NMJ in ALS pathogenesis. We have emphasized the molecular alterations in cellular components of NMJ leading to loss of effective neuromuscular transmission in ALS. Further, we provide a preview into research involved in exploring NMJ as potential target for designing effective therapies for ALS.

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