Neurological diseases present an immense burden on global healthcare systems, accounting for an increasing number of disability-adjusted life years. Mounting evidence suggests that dysregulated immune responses, specifically inflammation, are key contributors to the development and progression of various neurological disorders. Inflammasomes, innate immune signaling platforms, have recently gained significant attention due to their involvement in the pathogenesis of numerous diseases. This review aims to provide a comprehensive analysis of inflammasome activation, with a specific focus on the role of inflammation resulting from multiple inflammasome types and the formation of ASC specks in the pathogenesis of neurological diseases.
Inflammasome Activation and Neural Inflammation:The inflammasome complex comprises a sensor protein, an adapter molecule, and an effector caspase, which collectively regulate the processing and release of highly inflammatory cytokines such as interleukin-1β (IL-1β) and IL-18. We will outline the various types of inflammasomes implicated in neurological diseases, including NLRP3, NLRC4, AIM2, and absent in melanoma 2 (AIM2) inflammasomes. Additionally, we will explore the role of ASC specks, which form through the polymerization of adapter protein ASC and facilitate inflammasome activation, leading to neuroinflammation.
Inflammasome Activation in Neurodegenerative Disorders:Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, are characterized by the progressive loss of neurons within specific brain regions. Emerging evidence suggests that inflammasome activation plays a crucial role in the neuroinflammation observed in these disorders. We will review the mechanisms through which inflammasome activation contributes to the deposition of amyloid-beta plaques and α-synuclein aggregates, leading to neuronal death and cognitive decline.
Inflammasome Activation in Neuroinflammatory Diseases:Neuroinflammatory diseases encompass a broad range of conditions, including multiple sclerosis and stroke, where inflammation serves a pathological role in disease development and progression. We will discuss the involvement of inflammasome activation in driving the recruitment and activation of inflammatory cells within the central nervous system. Moreover, we will examine the interplay between inflammasome activation and oligodendrocyte damage, demyelination, and axonal degeneration in the context of neuroinflammatory diseases.
Therapeutic Perspectives and Conclusion:The multifaceted involvement of inflammasome activation in numerous neurological diseases provides a promising target for therapeutic interventions. We will highlight potential strategies to modulate inflammasome activation, ranging from small molecules to biological agents. Additionally, we will present emerging nanoparticle-based interventions that hold the potential to specifically target inflammasome complexes within the central nervous system. Overall, unraveling the complexity of inflammasome activation in neurological diseases could pave the way for novel treatment approaches, aiming to mitigate neuroinflammation and halt disease progression.
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