Interaction between autophagy and the NLRP3 inflammasome in Alzheimer’s and Parkinson’s disease

Abstract

Autophagy degrades phagocytosed damaged organelles, misfolded proteins, and various pathogens through lysosomes as an essential way to maintain cellular homeostasis. Autophagy is a tightly regulated cellular self-degradation process that plays a crucial role in maintaining normal cellular function and homeostasis in the body. The NLRP3 inflammasome in neuroinflammation is a vital recognition receptor in innate cellular immunity, sensing external invading pathogens and endogenous stimuli and further triggering inflammatory responses. The NLRP3 inflammasome forms an inflammatory complex by recognizing DAMPS or PAMPS, and its activation triggers caspase-1-mediated cleavage of pro-IL-1β and pro-IL-18 to promote the inflammatory response. In recent years, it has been reported that there is a complex interaction between autophagy and neuroinflammation. Strengthening autophagy can regulate the expression of NLRP3 inflammasome to reduce neuroinflammation in neurodegenerative disease and protect neurons. However, the related mechanism is not entirely clear. The formation of protein aggregates is one of the standard features of Neurodegenerative diseases. A large number of toxic protein aggregates can induce inflammation. In theory, activation of the autophagy pathway can remove the potential toxicity of protein aggregates and delay the progression of the disease. This article aims to review recent research on the interaction of autophagy, NLRP3 inflammasome, and protein aggregates in Alzheimer’s disease (AD) and Parkinson’s disease (PD), analyze the mechanism and provide theoretical references for further research in the future.

Hydroxytyrosol Interference with Inflammaging via Modulation of Inflammation and Autophagy

“…In addition, AMPK can inhibit the inflammatory response by inhibiting the pro-inflammatory NF-κB pathway in immune and non-immune cells [ 158 ]. Furthermore, enabling the removal of damaged cell material, autophagy also regulates the intracellular danger signal-sensing multiprotein platform such as the NLRP3 inflammasome, inhibiting thus the activation of IL-1β and IL-18 inflammatory cytokines [ 159 , 160 ]. Finally, autophagy regulates also the adaptive immune response, such as T lymphocyte function, including their metabolism, survival, development, proliferation, differentiation and aging.…”

Epigenetic regulation of autophagy in neuroinflammation and synaptic plasticity

“…Accumulation of misfolded and aggravated proteins is one of the common features of most neurodegenerative diseases ( 3 ). The fundamental function of autophagy is to clear damaged organelles, protein aggregates, or lipid droplets, the accumulation of which, when autophagy is downregulated, impairs brain cell functions and induce neuroinflammation ( 3 , 125 ).…”

Exploring Inflammasome Complex as a Therapeutic Approach in Inflammatory Diseases

“…In addition to their role in inducing neuroinflammation and Aβ deposition, inflammasomes have been implicated in other pathological processes, such as tau hyperphosphorylation and autophagy [110]. Tau hyperphosphorylation is a crucial pathological process in AD closely associated with the formation of neurofibrillary tangles (NFTs), a hallmark of AD pathology.…”