Functional microglia neurotransmitters in amyotrophic lateral sclerosis

Today neuroscience is dominated by the perspective that microglia are essential elements in any integrated view of the nervous system. A number of different neuroinflammatory conditions affect the CNS where microglia involvement, and particularly microgliosis, is not only a prominent feature, but also a pathogenic key mechanism of disease. On the other side, microglia can also constitute an important trigger of neuronal protection during neurodegenerative disorders. For instance in ALS and other motor neuron diseases, available evidence suggests the coexistence of quite different roles for microglia, characterized by neuroprotective functions at early stages, and neurotoxic actions during disease progression. The scope of this review is a brief discussion about microglia being activated and functioning during ALS, and particularly about neurotransmitters participating to the pathological signature of ALS microglia. We will discuss that ALS microglia can express a variety of classical neurotransmitter receptors comprising those for extracellular ATP, glutamate and histamine. We will review data indicating that the modulation of these transmitter receptors may induce beneficial effects in ALS models, so that the protective properties of microglia can be emphasized at the expenses of their toxicity.