Role of dietary fatty acids in microglial polarization in Alzheimer’s disease

Abstract

Microglial polarization is an utmost important phenomenon in Alzheimer's disease that influences the brain environment. Polarization depends upon the types of responses that cells undergo, and it is characterized by receptors present on the cell surface and the secreted cytokines to the most. The expression of receptors on the surface is majorly influenced by internal and external factors such as dietary lipids. Types of fatty acids consumed through diet influence the brain environment and glial cell phenotype and types of receptors on microglia. Reports suggest that dietary habits influence microglial polarization and the switching of microglial phenotype is very important in neurodegenerative diseases. Omega-3 fatty acids have more influence on the brain, and they are found to regulate the inflammatory stage of microglia by fine-tuning the number of receptors expressed on microglia cells. In Alzheimer's disease, one of the pathological proteins involved is Tau protein, and microtubuleassociated protein upon abnormal phosphorylation detaches from the microtubule and forms insoluble aggregates. Aggregated proteins have a tendency to propagate within the neurons and also become one of the causes of neuroinflammation. We hypothesize that tuning microglia towards anti-inflammatory phenotype would reduce the propagation of Tau in Alzheimer's disease.

Plasma dilution improves cognition and attenuates neuroinflammation in old mice

“…Recent studies show that experimental brain injuries in mice negatively affect hippocampal health (loss of synapses, neuronal death) and impact cognition even when the foci of such injuries and subsequent microglia activation are elsewhere in the brain [95][96][97][98]. Moreover, local microglia activation leads to broad inflammatory responses in the brain through autocrine and paracrine functions of the pro-inflammatory secretome, which cumulatively increases neuroinflammation throughout the brain [99,100]. In concert with our findings, an injury sustained in the thalamus (e.g., one of the regions where we found an age-associated, NBE reduced neuroinflammation) activates microglia and perpetuates neurodegeneration and cognitive decline [101].…”

Multimodal single-cell/nucleus RNA-sequencing data analysis uncovers molecular networks between disease-associated microglia and astrocytes with implications for drug repurposing in Alzheimer’s disease

“…where j = 1, 2, …, s were the gene sets from molecular network sorted in ascending order by their rank in the gene profiles of the drug being evaluated. The rank of gene j is denoted by V(j), where 1 ≤ ( ) ≤ , with r being the number of genes (12,849) (8) In the above equations, Further, we excluded observations that started within 180-day of insurance enrollment.…”

“…and ORM2) and help microglia modulate astrocytic phenotypes and functions (e.g., IL-1 and TNF-) 11 . A growing body of evidence suggests that both microglia and astrocytes are exquisitely sensitive to their environment that can be affected by the dysregulation of multiple biochemical pathways, such as abnormal lipid metabolism, in AD pathogenesis 12 .…”

α-Linolenic acid induces clearance of Tau seed via Actin-remodeling in Microglia

“…The extracellular species of Tau can exert toxicity in cultured hippocampal neurons via unbalanced calcium metabolism and causes cell death [7]. Polyunsaturated [8][9][10]. Omega-3 fatty acids are known to exert anti-in ammatory effect on brain cells.…”