Granzymes in Neuroinflammation and Neurodegenerative Diseases

Abstract Neuroinflammation is a central driver of numerous neurological disorders. While granzymes have classically been studied as cytotoxic effector molecules secreted from immune cells along with the pore-forming molecule, perforin, accumulating evidence suggests that these serine proteases also play roles in non-cytotoxic, neuroinflammatory processes. This review summarizes the current and emerging paradigms related to how granzymes contribute to the progression of neuroinflammation and neurological diseases. Taken together, current research supports a pathogenic role for granzymes as key mediators linking immune activation to neuronal damage and sustained neuroinflammation. Investigating granzyme-modulated neuroinflammatory responses in the CNS may unveil new avenues for therapeutic intervention in neuroinflammatory and neurodegenerative disorders.