Role of pyroptosis in the pathogenesis of various neurological diseases

Abstract

Pyroptosis, an inflammatory programmed cell death process, has recently garnered significant attention due to its pivotal role in various neurological diseases. This review delves into the intricate molecular signaling pathways governing pyroptosis, encompassing both caspase-1 dependent and caspase-1 independent routes, while emphasizing the critical role played by the inflammasome machinery in initiating cell death. Notably, we explore the Nucleotide-binding domain leucine-rich repeat (NLR) containing protein family, the Absent in melanoma 2-like receptor family, and the Pyrin receptor family as essential activators of pyroptosis. Additionally, we comprehensively examine the Gasdermin family, renowned for their role as executioner proteins in pyroptosis. Central to our review is the interplay between pyroptosis and various central nervous system (CNS) cell types, including astrocytes, microglia, neurons, and the blood-brain barrier (BBB). Pyroptosis emerges as a significant factor in the pathophysiology of each cell type, highlighting its far-reaching impact on neurological diseases. This review also thoroughly addresses the involvement of pyroptosis in specific neurological conditions, such as HIV infection, drug abuse-mediated pathologies, Alzheimer's disease, and Parkinson's disease. These discussions illuminate the intricate connections between pyroptosis, chronic inflammation, and cell death in the development of these disorders. We also conducted a comparative analysis, contrasting pyroptosis with other cell death mechanisms, thereby shedding light on their unique aspects. This approach helps clarify the distinct contributions of pyroptosis to neuroinflammatory processes. In conclusion, this review offers a comprehensive exploration of the role of pyroptosis in various neurological diseases, emphasizing its multifaceted molecular mechanisms within various CNS cell types. By elucidating the link between pyroptosis and chronic inflammation in the context of neurodegenerative disorders and infections, it provides valuable insights into potential therapeutic targets for mitigating these conditions.

Keywords: Gasdermin; Inflammasomes; Neurodegenerative diseases; Neuroinflammation; Pyroptosis.