Figure 3. Inflammasome activation in neurodegenerative disease.

Inflammasomes can be activated in the CNS in response to acute injury (traumatic brain injury and stroke), autoimmune‐mediated injury (multiple sclerosis), and accumulation of misfolded or aggregated proteins in the brain (Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and prion disease). Inflammasome activation has been demonstrated in CNS‐resident cell types, including microglia, astrocytes, and neurons, but also in CNS‐infiltrating cells, such as in infiltrating macrophages. Although most research on neurodegenerative diseases has focused on the importance of the NLRP3 inflammasome, also other inflammasome types can be activated in the brain and have been demonstrated in neurodegenerative disorders. Overall, inflammasome activation results in caspase‐1‐mediated cleavage of pro‐IL‐1β and pro‐IL‐18, and the subsequent release of the mature cytokines. High levels of IL‐1β and IL‐18 can be detected in many neurodegenerative conditions and are considered to be crucial for the establishment of a chronic inflammatory environment, leading to neuronal dysfunction and eventually neurodegeneration.