Neuroinflammatory Signaling in the Pathogenesis of Alzheimer’s Disease

Abstract

: Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the formation of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques. Growing evidence has suggested that AD pathogenesis is not only limited to the neuronal compartment but also strongly interacts with immunological processes in the brain. On the other hand, aggregated and misfolded proteins can bind with pattern recognition receptors located on astroglia and microglia and can in turn induce an innate immune response, characterized by the release of inflammatory mediators, ultimately playing a role in both the severity and the progression of the disease. It has been reported by genome-wide analysis that several genes which elevate the risk for sporadic AD encode for factors controlling the inflammatory response and glial clearance of misfolded proteins. Obesity and systemic inflammation are examples of external factors which may interfere with the immunological mechanisms of the brain and can induce disease progression. In this review, we discussed the mechanisms and essential role of inflammatory signaling pathways in AD pathogenesis. Indeed, interfering with immune processes and modulation of risk factors may lead to future therapeutic or preventive AD approaches.

Low Xanthophylls, Retinol, Lycopene, and Tocopherols in Grey and White Matter of Brains with Alzheimer’s Disease

“…Current models of pathogenesis focus on mitochondrial dysfunction [5][6][7], disrupted autophagy of aged or damaged organelles, particularly mitochondria [8,9], protein misfolding following S-nitrosylation or oxidation [10], or production of inflammatory cytokines and reactive oxygen species by microglia and astrocytes around amyloid plaques or neurofibrillary tangles [11]. All models include oxidative damage in the pathogenesis and progression of AD [12][13][14] and end with neuroinflammation and neuronal death [14,15].…”

Molecular Mechanisms of Inflammasome in Ischemic Stroke Pathogenesis

“…It also determines an increased expression of chemokines and stimulates the migration of leukocytes into the cerebral parenchyma. IL-18 also causes an augmented chemokine and adhesion molecules production in T-helper 1 (Th1), B cells, and NK (natural killer) cells [ 50 ]. In addition, the cytokine above-mentioned induces the expression of Fas ligand in glial cells, thereby exacerbating neuroinflammation and neuronal death [ 42 ].…”

Reducing PDK1/Akt Activity: An Effective Therapeutic Target in the Treatment of Alzheimer’s Disease

“…Innate immune activation, including the neuroinflammatory response, possibly affects the occurrence of AD and its pathogenicity [ 90 , 91 , 92 ]. For example, immune receptors such as the cluster of differentiation 33 (CD33), clusterin (CLU), complement receptor 1 (CR1), and the triggering receptor expressed on myeloid cells 2 (TREM2) are related to AD progression, as reported by genome-wide association studies (GWAS) [ 93 ].…”