Functional and structural damage of neurons by innate immune mechanisms during neurodegeneration

Over the past decades, our view on neurodegenerative diseases has been mainly centered around neurons and their networks. Only recently it became evident that immunological processes arise alongside degenerating neurons, raising the question whether these represent just meaningless bystander reactions or in turn, contribute to pathogenesis and disease symptoms. When considering any effect of inflammatory events on the CNS one has to consider the site, duration and nature of immune activation. Likewise, one has to distinguish between mechanisms which directly impact the neuronal compartment and indirect mechanisms, which affect cells that are important for neuronal functioning and survival. As discussed in this review, both types of mechanisms may be present at the same time and additively or synergistically lead to neuronal demise. Inflammatory mediators released by the principle innate immune cells of the brain, microglia and astrocytes, can compromise the function and structure of neurons, thereby playing important roles in the pathogenesis of neurodegenerative diseases.