The Role of Inflammasomes in the Pathogenesis of Neurodegenerative Diseases

Abstract

—Protein misfolding and accumulation of protein aggregates is a distinctive feature of most neurodegenerative diseases. They lead to disruption of cellular homeostasis, loss of synaptic connections, and therefore cellular apoptosis. It has been demonstrated that some innate immune responses play an important role in the emergence and progression of neurodegenerative diseases. Inflammasomes are components of innate immunity that play a major role in the maintenance of chronic inflammation. Inflammasomes function as intracellular sensors, detecting both exogenous and endogenous stimuli. They also take part in caspase-1 activation and the synthesis of pro-inflammatory cytokines. In the central nervous system (CNS), inflammasomes are predominantly expressed by microglia, the key cells of innate immunity responsible for activation and maintenance of inflammation. In addition to microglia, inflammasomes can be expressed and activated by astrocytes and neurons, as well as infiltrating myeloid cells. Understanding the mechanisms of activation and functioning of inflammasomes is crucial for the development of novel drugs targeted at modulation of the immune response associated with their excessive activation. This review provides up-to-date information on the inflammasome structure and mechanisms of action, the role of protein misfolding, aggregation and the influence of these factors on inflammasome activation, as well as potential therapeutic targets in neurodegenerative diseases.