Deletion of the inflammatory S100-A9/MRP14 protein does not influence survival in hSOD1G93A ALS mice

Abstract

Neuroinflammation is a hallmark of Amyotrophic Lateral Sclerosis (ALS) in hSOD1^G93A mouse models where microglial cells contribute to the progressive motor neuron degenerative process. S100-A8 and S100-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 hSOD1^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 S100-A9 would not be a valuable strategy for ALS.

Keywords: ALS; Calgranulin B; DAMP; Neuroinflammation; S100a9/MRP14.