Signalling Pathways Involved in Microglial Activation in Alzheimer’s Disease and Potential Neuroprotective Role of Phytoconstituents

Abstract

Alzheimer’s disease (AD) is a commonly reported neurodegenerative disorder associated with dementia and cognitive impairment. The pathophysiology of AD comprises Aβ, hyperphosphorylated tau protein formation, abrupt cholinergic cascade, oxidative stress, neuronal apoptosis, and neuroinflammation. Recent findings have established the profound role of immunological dysfunction and microglial activation in the pathogenesis of AD. Microglial activation is a multifactorial cascade encompassing various signalling molecules and pathways such as Nrf2/NLRP3/NF-kB/p38 MAPKs/ GSK-3β. Additionally, deposited Aβ or tau protein triggers microglial activation and accelerates its pathogenesis. Currently, the FDA-approved therapeutic regimens are based on the modulation of the cholinergic system, and recently, one more drug, aducanumab, has been approved by the FDA. On the one hand, these drugs only offer symptomatic relief and not a cure for AD. Additionally, no targeted-based microglial medicines are available for treating and managing AD. On the other hand, various natural products have been explored for the possible anti-Alzheimer effect via targeting microglial activation or different targets of microglial activation. Therefore, the present review focuses on exploring the mechanism and associated signalling related to microglial activation and a detailed description of various natural products that have previously been reported with anti-Alzheimer’s effect via mitigation of microglial activation. Additionally, we have discussed the various patents and clinical trials related to managing and treating AD.

Effects of Probiotics on Colitis-Induced Exacerbation of Alzheimer’s Disease in AppNL-G-F Mice

“…Interestingly, DSS increased soluble Aβ 1-40 concentrations compared to vehicle controls, although neither treatment alone produced significant differences compared to the vehicle group for either peptide (Figure 5). Microglial activation is also hypothesized to have a role in AD pathophysiology [52][53][54][55].…”

“…To investigate whether probiotic and/or DSS treatment altered astrogliosis, brain sections were immunostained for the glial acidic fibrillary protein (GFAP). In WT mice, a basal level of Microglial activation is also hypothesized to have a role in AD pathophysiology [52][53][54][55]. To examine the effect of DSS-induced colitis and the probiotic treatments on microglial reactivity, mouse brain sections were immunostained for the ionized calcium-binding adapter molecule 1 (Iba1) protein.…”