Impacts of H2O2, SARM1 inhibition, and high NAm concentrations on Huntington's disease laser‐induced degeneration

Author:

Barber Sophia12,Gomez‐Godinez Veronica1,Young Joy1,Wei Abigail1,Chen Sarah1,Snissarenko Anna2,Chan Sze Sze2,Wu Chengbiao12,Shi Linda1ORCID

Affiliation:

1. Institute of Engineering in Medicine University of California San Diego La Jolla California USA

2. Department of Neurosciences University of California San Diego La Jolla California USA

Abstract

AbstractAxonal degeneration is a key component of neurodegenerative diseases such as Huntington's disease (HD), Alzheimer's disease, and amyotrophic lateral sclerosis. Nicotinamide, an NAD+ precursor, has long since been implicated in axonal protection and reduction of degeneration. However, studies on nicotinamide (NAm) supplementation in humans indicate that NAm has no protective effect. Sterile alpha and toll/interleukin receptor motif‐containing protein 1 (SARM1) regulates several cell responses to axonal damage and has been implicated in promoting neuronal degeneration. SARM1 inhibition seems to result in protection from neuronal degeneration while hydrogen peroxide has been implicated in oxidative stress and axonal degeneration. The effects of laser‐induced axonal damage in wild‐type and HD dorsal root ganglion cells treated with NAm, hydrogen peroxide (H2O2), and SARM1 inhibitor DSRM‐3716 were investigated and the cell body width, axon width, axonal strength, and axon shrinkage post laser‐induced injury were measured.

Publisher

Wiley

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