Absence of Receptor for Advanced Glycation End Product (RAGE) Reduces Inflammation and Extends Survival in the hSOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis.

Molecular Neurobiology
John D LeeTrent M Woodruff

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing motor neuron degenerative disease that is without effective treatment. The receptor for advanced glycation end products (RAGE) is a major component of the innate immune system that has been implicated in ALS pathogenesis. However, the contribution of RAGE signalling to the neuroinflammation that underlies ALS neurodegeneration remains unknown. The present study therefore generated SOD1G93A mice lacking RAGE and compared them with SOD1G93A transgenic ALS mice in respect to disease progression (i.e. body weight, survival and muscle strength), neuroinflammation and denervation markers in the spinal cord and tibialis anterior muscle. We found that complete absence of RAGE signalling exerted a protective effect on SOD1G93A pathology, slowing disease progression and significantly extending survival by ~ 3 weeks and improving motor function (rotarod and grip strength). This was associated with reduced microgliosis, cytokines, innate immune factors (complement, TLRs, inflammasomes), and oxidative stress in the spinal cord, and a reduction of denervation markers in the tibialis anterior muscle. We also documented that RAGE mRNA expression was significantly increased ...Continue Reading

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Citations

Feb 16, 2021·Human Immunology·João Rodrigues Lima-JuniorAlessandro Sette
May 28, 2021·Neurobiology of Aging·Margarita GerouScott P Allen
Jun 18, 2021·Cellular and Molecular Neurobiology·Alejandro F De NicolaMaria Claudia Gonzalez Deniselle

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Methods Mentioned

BETA
PCR
genotyping
transgenic

Software Mentioned

GraphPad Prism

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