SARM1-mediated wallerian degeneration: A possible mechanism underlying organophosphorus-induced delayed neuropathy.

Abstract

Some organophosphorus compounds (OPs) can cause a type of delayed neurotoxicity in human being, which is known as organophosphorus-induced delayed neuropathy (OPIDN). Signs and symptoms of the patients include tingling and sensory loss of the hands and feet, followed by progressive muscle weakness in the lower and upper limbs, and ataxia. Pathologically, OPIDN are characterized by distal sensorimotor axonopathy due to the distal axonal degeneration of nerve tracts located in central and peripheral nervous systems. The morphological pattern of the distal axonopathy is similar to Wallerian degeneration that occurs after nerve injury in vitro. It is generally acknowledged that inhibition and subsequent aging of neuropathy target esterase (NTE) is required for the occurrence of OPIDN. However, the underlying mechanisms through which NTE triggers axonal degeneration in OPIDN is still largely unclear. Recently, sterile alpha and toll/interleukin receptor motif-containing protein 1（SARM1) has been identified as a key player in Wallerian degeneration. In physical and chemical transection of axons, SARM1 was found to promotes axon degeneration by hydrolyzing NAD+. By contrast, SARM1 deficiency could prevent neuron degeneration in response to a wide range of insults. Furthermore, SARM1 can also translocate to mitochondria and cause mitochondrial damage, thus triggering axon degeneration and neuron death. These findings suggested the existence of a pathway in axonal degeneration that might be targeted therapeutically. Here, we hypothesize that SARM1 activation after NTE inhibition and aging might be an etiological factor in OPIDN that regulates Wallerian-like degeneration. Analysing SARM1 mediated NAD degeneration pathway and its upstream activators in OPIDN could contribute to the development of novel therapies to treat OPIDN.

• Authors: Mingxue Song, Kang Kang, Fuyong Song
• Journal: Medical hypotheses (Med Hypotheses) Vol. 155 Pg. 110666 (Oct 2021) ISSN: 1532-2777 [Electronic] United States
• PMID: 34455132 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier Ltd.

Chemical References

• Armadillo Domain Proteins
• Cytoskeletal Proteins
• SARM1 protein, human

Topics

• Armadillo Domain Proteins
• Axons (pathology)
• Cytoskeletal Proteins
• Humans
• Peripheral Nervous System Diseases
• Wallerian Degeneration (chemically induced, pathology)