The role of immune-mediated alterations and disorders in ALS disease

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that leads to neuronal death in the brain and spinal cord. Over the last decades, evidence has emerged regarding the functional diversity of astrocytes, microglia, and T cells in the central nervous system (CNS), and the role of neuroinflammation in ALS. In this review, we summarize current knowledge regarding neuroinflammation in ALS, both at the level of specific molecular pathways and potential cellular pathways as well as outline questions about the immune mechanisms involved in ALS pathogenesis.

Keywords: ALS; Autoimmunity; Glial cells; Neuroinflammation.

Figure 1.. CD4⁺ T cell reactivity in ALS disease.

Misfolded protein aggregates are taken up by dendritic cells and reach the draining lymph nodes, where proteins can be presented as self-peptides through MHC class II for recognition by CD4⁺ T cells. After priming, antigen-specific T cells migrate to the CNS. Upon activation, microglia upregulate MHC class II and act as antigen-presenting cells to restimulate CNS-infiltrating T cells, promoting neuroinflammation.