The involvement of NLRP3 inflammasome in the treatment of neurodegenerative diseases

Biomed Pharmacother. 2021 Jun:138:111428. doi: 10.1016/j.biopha.2021.111428. Epub 2021 Mar 2.

Abstract

In an ageing society, neurodegenerative diseases have attracted attention because of their high incidence worldwide. Despite extensive research, there is a lack of conclusive insights into the pathogenesis of neurodegenerative diseases, which limit the strategies for symptomatic treatment. Therefore, better elucidation of the molecular mechanisms involved in neurodegenerative diseases can provide an important theoretical basis for the discovery of new and effective prevention and treatment methods. The innate immune system is activated during the ageing process and in response to neurodegenerative diseases. Inflammasomes are multiprotein complexes that play an important role in the activation of the innate immune system. They mediate inflammatory reactions and pyroptosis, which are closely involved in neurodegeneration. There are different types of inflammasomes, although the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is the most common inflammasome; NLRP3 plays an important role in the pathogenesis of neurodegenerative diseases. In this review, we will discuss the mechanisms that are involved in the activation of the NLRP3 inflammasome and its crucial role in the pathology of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis. We will also review various treatments that target the NLRP3 inflammasome pathway and alleviate neuroinflammation. Finally, we will summarize the novel treatment strategies for neurodegenerative disorders.

Keywords: Alzheimer’s disease; Amyotrophic lateral sclerosis; Multiple sclerosis; NLRP3 inflammasome; Parkinson's disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends
  • Humans
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism*
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / metabolism
  • Treatment Outcome

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Neuroprotective Agents