Neuroinflammation in motor neuron disease

Abstract

Neuroinflammation, which is characterized by activated microglia, astrocytes, infiltrating immune cells and the subsequent production of inflammatory mediators, is linked to a pathological process common to neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis (ALS). Furthermore, increasing evidence suggests that activated glial cells and immune cells surrounding motor neurons also contribute to the non-cell autonomous neurodegeneration through neuroinflammation mediated by these non-neuronal cells. As activated microglia can produce pro-inflammatory cytokines and other neurotoxic or protective molecules under the control of infiltrated T cells and astrocytes, neuroinflammation includes both the detrimental and beneficial effects on motor neurons. Activated astrocytes also have an important role in neuroinflammation in ALS by interfering with the beneficial effects of neuroinflammation partly by transforming growth factor-β1. In the peripheral blood of ALS patients, CD4+ T cells might have a tendency to polarize toward pro-inflammatory type 1 T helper cells, and regulatory T cells are decreased during disease progression in ALS. Many ongoing clinical trials for ALS targeting neuroinflammation, together with a further understanding of the role of neuroinflammation in disease, will lead to the development of novel therapeutics for ALS.