Deletion of the inflammatory S100-A9/MRP14 protein does not influence survival in hS0D1G93A ALS mice

Neuroinflammation is a hallmark of Amyotrophic Lateral Sclerosis (ALS) in hS0D1(G93A) mouse models where microglial cells contribute to the progressive motor neuron degenerative process. 5100-A8 and 5100-A9 (also known as MRP8 and MRP14, respectively) are cytoplasmic proteins expressed by inflammatory myeloid cells, including microglia and macrophages. Mainly acting as a heterodimer, S100-A8/A9, when secreted, can activate Toll-like Receptor 4 on immune cells, leading to deleterious proinflammatory cytokine production. Deletion of S100a9 in Alzheimer's disease mouse models showed a positive outcome, reducing pathology. We now assessed its role in ALS. Unexpectedly, our results show that deleting S100a9 in hS0D1(G93A) ALS mice had no impact on mouse survival, but rather accelerated symptoms with no impact on microglial activation and motor neuron survival, suggesting that blocking 5100-A9 would not be a valuable strategy for ALS. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

Neuroinflammation is a hallmark of ALS, where deletion of S100a9 did not improve mouse survival but instead accelerated symptoms, indicating that blocking 5100-A9 is not a viable strategy for treating ALS.