Innate Immune Cell Death in Neuroinflammation and Alzheimer's Disease

被引:128
作者
Rajesh, Yetirajam [1 ]
Kanneganti, Thirumala-Devi [1 ]
机构
[1] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA
基金
美国国家卫生研究院;
关键词
neuroinflammation; innate immunity; cell death; pyroptosis; apoptosis; necroptosis; inflammasome; caspase-1; caspase-3; caspase-6; caspase-7; caspase-8; caspase-9; RIPK1; RIPK3; ZBP1; NLRP3; AIM2; MLKL; Toll-like receptor; PANoptosis; PANoptosome; Alzheimer's disease; Amyloid beta; Tau; microglia; MIXED LINEAGE KINASE; BETA PRECURSOR PROTEIN; NECROSIS-FACTOR-ALPHA; AMYLOID-BETA; INFLAMMASOME ACTIVATION; MICROGLIAL ACTIVATION; MOUSE MODEL; NLRP3; INFLAMMASOME; MOLECULAR-MECHANISMS; DOMAIN-LIKE;
D O I
10.3390/cells11121885
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Alzheimer's disease (AD) is a neurodegenerative disorder molecularly characterized by the formation of amyloid beta (A beta) plaques and type 2 microtubule-associated protein (Tau) abnormalities. Multiple studies have shown that many of the brain's immunological cells, specifically microglia and astrocytes, are involved in AD pathogenesis. Cells of the innate immune system play an essential role in eliminating pathogens but also regulate brain homeostasis and AD. When activated, innate immune cells can cause programmed cell death through multiple pathways, including pyroptosis, apoptosis, necroptosis, and PANoptosis. The cell death often results in the release of proinflammatory cytokines that propagate the innate immune response and can eliminate A beta plaques and aggregated Tau proteins. However, chronic neuroinflammation, which can result from cell death, has been linked to neurodegenerative diseases and can worsen AD. Therefore, the innate immune response must be tightly balanced to appropriately clear these AD-related structural abnormalities without inducing chronic neuroinflammation. In this review, we discuss neuroinflammation, innate immune responses, inflammatory cell death pathways, and cytokine secretion as they relate to AD. Therapeutic strategies targeting these innate immune cell death mechanisms will be critical to consider for future preventive or palliative treatments for AD.
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页数:25
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