RESUMEN
Neuroinflammation is a hallmark of Amyotrophic Lateral Sclerosis (ALS) in hSOD1G93A 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 hSOD1G93A 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.
