Microglia in neurodegenerative disease

Microglia, the resident macrophages of the CNS, are exquisitely sensitive to brain injury and disease, altering their morphology and phenotype to adopt a so-called activated state in response to pathophysiological brain insults. Morphologically activated microglia, like other tissue macrophages, exist as many different phenotypes, depending on the nature of the tissue injury. Microglial responsiveness to injury suggests that these cells have the potential to act as diagnostic markers of disease onset or progression, and could contribute to the outcome of neurodegenerative diseases. The persistence of activated microglia long after acute injury and in chronic disease suggests that these cells have an innate immune memory of tissue injury and degeneration. Microglial phenotype is also modified by systemic infection or inflammation. Evidence from some preclinical models shows that systemic manipulations can ameliorate disease progression, although data from other models indicates that systemic inflammation exacerbates disease progression. Systemic inflammation is associated with a decline in function in patients with chronic neurodegenerative disease, both acutely and in the long term. The fact that diseases with a chronic systemic inflammatory component are risk factors for Alzheimer disease implies that crosstalk occurs between systemic inflammation and microglia in the CNS

: Motor neuron-immune interactions

International audienceBecause microglial cells, the resident macrophages of the CNS, react to any lesion of the nervous system, they have for long been regarded as potential players in the pathogenesis of several neurodegenerative disorders including amyotrophic lateral sclerosis, the most common motor neuron disease in the adult. In recent years, this microglial reaction to motor neuron injury, in particular, and the innate immune response, in general, has been implicated in the progression of the disease, in mouse models of ALS. The mechanisms by which microglial cells influence motor neuron death in ALS are still largely unknown. Microglial activation increases over the course of the disease and is associated with an alteration in the production of toxic factors and also neurotrophic factors. Adding to the microglial/macrophage response to motor neuron degeneration, the adaptive immune system can likewise influence the disease process. Exploring these motor neuron-immune interactions could lead to a better understanding in the physiopathology of ALS to find new pathways to slow down motor neuron degeneration