Innate Immune Cell Death in Neuroinflammation and Alzheimer's Disease.
Yetirajam RajeshThirumala-Devi KannegantiPublished in: Cells (2022)
Alzheimer's disease (AD) is a neurodegenerative disorder molecularly characterized by the formation of amyloid β (Aβ) 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 Aβ 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.
Keyphrases
- immune response
- cell death
- cell cycle arrest
- innate immune
- cerebral ischemia
- traumatic brain injury
- lipopolysaccharide induced
- dendritic cells
- toll like receptor
- induced apoptosis
- lps induced
- cognitive impairment
- pi k akt
- inflammatory response
- cognitive decline
- oxidative stress
- white matter
- endoplasmic reticulum stress
- palliative care
- multiple sclerosis
- subarachnoid hemorrhage
- signaling pathway
- brain injury
- drug induced
- antimicrobial resistance
- case control