Abstract
Inflammasomes are molecular scaffolds that are activated by damage-associated and pathogen-associated molecular patterns and form a key element of innate immune responses. Consequently, the involvement of inflammasomes in several diseases that are characterized by inflammatory processes, such as multiple sclerosis, is widely appreciated. However, many other neurological conditions, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, stroke, epilepsy, traumatic brain injury, sepsis-associated encephalopathy and neurological sequelae of COVID-19, all involve persistent inflammation in the brain, and increasing evidence suggests that inflammasome activation contributes to disease progression in these conditions. Understanding the biology and mechanisms of inflammasome activation is, therefore, crucial for the development of inflammasome-targeted therapies for neurological conditions. In this Review, we present the current evidence for and understanding of inflammasome activation in neurological diseases and discuss current and potential interventional strategies that target inflammasome activation to mitigate its pathological consequences.
Key points
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Inflammasomes are key molecular scaffolds that mediate innate immune responses.
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Many neurological conditions involve an underlying chronic inflammatory process that worsens the trajectory of these conditions.
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Increased activation of NLRP3 and other inflammasomes, leading to increases in IL-1β and IL-18 and neuronal damage, is seen in post-mortem brain tissue from people with neurological conditions.
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Genetic ablation and synthetic inhibition of inflammasomes and inflammasome-associated proteins can ameliorate neurological deficits in rodent models of neurological conditions.
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Use of inflammasome-targeted therapeutic approaches could improve existing therapeutic strategies for multiple neurological conditions.
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Ravichandran, K.A., Heneka, M.T. Inflammasomes in neurological disorders — mechanisms and therapeutic potential. Nat Rev Neurol 20, 67–83 (2024). https://doi.org/10.1038/s41582-023-00915-x
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DOI: https://doi.org/10.1038/s41582-023-00915-x
