The Role of the Effects of Autophagy on NLRP3 Inflammasome in Inflammatory Nervous System Diseases

Abstract

Autophagy is a stable self-sustaining process in eukaryotic cells. In this process, pathogens, abnormal proteins, and organelles are encapsulated by a bilayer membrane to form autophagosomes, which are then transferred to lysosomes for degradation. Autophagy is involved in many physiological and pathological processes. Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, containing NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and pro-caspase-1, can activate caspase-1 to induce pyroptosis and lead to the maturation and secretion of interleukin-1 β (IL-1 β) and IL-18. NLRP3 inflammasome is related to many diseases. In recent years, autophagy has been reported to play a vital role by regulating the NLRP3 inflammasome in inflammatory nervous system diseases. However, the related mechanisms are not completely clarified. In this review, we sum up recent research about the role of the effects of autophagy on NLRP3 inflammasome in Alzheimer’s disease, chronic cerebral hypoperfusion, Parkinson’s disease, depression, cerebral ischemia/reperfusion injury, early brain injury after subarachnoid hemorrhage, and experimental autoimmune encephalomyelitis and analyzed the related mechanism to provide theoretical reference for the future research of inflammatory neurological diseases.

Protective Effects of Remimazolam on Cerebral Ischemia/Reperfusion Injury in Rats by Inhibiting of NLRP3 Inflammasome-Dependent Pyroptosis

“…It participates in regulating inflammatory cascades in multiple diseases, in the meantime, shows a role in pyroptosis by affecting pore-forming protein gasdermin D (GSDMD). 32 , 33 ; The activated NLRP3 will promote pro-caspase-1 to transform into caspase-1 of hydrolysis activity, in turn activating several proinflammatory cytokines including IL-1β and IL-18. 34 GSDMD is a specific effector molecule involved in pore channel formation and the N-terminal fragment function is the key for the occurrence of pyroptosis.…”

TI: NLRP3 Inflammasome-Dependent Pyroptosis in CNS Trauma: A Potential Therapeutic Target

“…Studies have shown that CTSB is an upstream activator of the NLRP3 inflammasome, promoting the release of IL-1β, and this effect can be inhibited by the CTSB inhibitor CA-074-Me5 (McHugh et al, 2019;Demirel et al, 2020). Additionally, CTSB inhibits autophagy by regulating the kinase ULK1 activity, and autophagy negatively regulates the activation of NLRP3 inflammasomes (Qi et al, 2016;Zhao et al, 2021). Similarly, recent evidence has illustrated that the use of autophagy inhibitors reversed the effect of betulinic acid, which reduces the activation of pyroptosis after SCI (Wu et al, 2021).…”

Targeting autophagy regulation in NLRP3 inflammasome-mediated lung inflammation in COVID-19

“…In recent years, increasing evidence has emphasized the importance of autophagy in limiting NLRP3 inflammasome-mediated excessive inflammation in various human diseases, such as neurodegenerative diseases, diabetes, and cardiovascular diseases [ [236] , [237] , [238] ]. In the past decade, many studies have proven that autophagy negatively regulates the activation of NLRP3 inflammasomes through various mechanisms.…”