Project Overview

Recently, Dr. Honglin Luo, in collaboration with Dr. Neil Cashman, discovered that mutations in the ALS-linked SOD1 gene result in activation of a specific neuroinflammatory pathway called cGAS-STING. Neuroinflammation is thought to play an important role in the progression of ALS and activation of this specific pathway has been identified in laboratory animal models of two other prominent causes of ALS, C9ORF72 and TDP-43.

With this grant, Drs. Luo and Cashman will further investigate how the cGAS-STING pathway is affected in SOD1-linked ALS using mice that have ALS mutations and either the cGAS or STING genes removed. This will help to determine if these pathways are critical to the motor neuron degeneration in SOD1 mice. They will also investigate the roles of cGAS and STING in the laboratory using cells expressing mutant forms of two other ALS-linked proteins, TDP-43 and FUS.

Ultimately this work will advance our understanding of the role of the cGAS-STING pathway in ALS disease progression and may reveal a promising new target for future therapies.