Neuroinflammation and Neurogenesis in Alzheimer’s Disease and Potential Therapeutic Approaches

Abstract

In adult brain, new neurons are generated throughout adulthood in the subventricular zone and the dentate gyrus; this process is commonly known as adult neurogenesis. The regulation or modulation of adult neurogenesis includes various intrinsic pathways (signal transduction pathway and epigenetic or genetic modulation pathways) or extrinsic pathways (metabolic growth factor modulation, vascular, and immune system pathways). Altered neurogenesis has been identified in Alzheimer’s disease (AD), in both human AD brains and AD rodent models. The exact mechanism of the dysregulation of adult neurogenesis in AD has not been completely elucidated. However, neuroinflammation has been demonstrated to alter adult neurogenesis. The presence of various inflammatory components, such as immune cells, cytokines, or chemokines, plays a role in regulating the survival, proliferation, and maturation of neural stem cells. Neuroinflammation has also been considered as a hallmark neuropathological feature of AD. In this review, we summarize current, state-of-the art perspectives on adult neurogenesis, neuroinflammation, and the relationship between these two phenomena in AD. Furthermore, we discuss the potential therapeutic approaches, focusing on the anti-inflammatory and proneurogenic interventions that have been reported in this field.

Role of Microglia in Modulating Adult Neurogenesis in Health and Neurodegeneration

“…However, further evidence is still required to fully address the mechanism mechanisms underlying microglial cell contribution in modulating neurogenesis in aging and neurodegenerative diseases, and to characterize the subsequent outcomes. A better understanding of the regulatory mechanisms that trigger microglial dysfunction during age and neurodegenerative diseases, including AD and PD, would allow the development of novel immunomodulatory therapeutic interventions that aim essentially to influence neurogenesis via modulation of microglial cell responses (reviewed in [ 255 ]).…”

20(S)-protopanaxadiol and oleanolic acid ameliorate cognitive deficits in APP/PS1 transgenic mice by enhancing hippocampal neurogenesis

“…Neuroinflammation plays an important role in the pathogenesis of AD. The neuroinflammatory process is responsive to neuronal loss and declining hippocampal neurogenesis, leading to dysregulation of hippocampus-dependent behaviors [ 28 ].…”

Neuroprotective Potentials of Panax Ginseng Against Alzheimer’s Disease: A Review of Preclinical and Clinical Evidences

“…Neuroinflammation is a continuous process that is implicated in the preclinical, moderate, and late stages of AD (Sung et al, 2020).…”

“…Neuroinflammation is a continuous process that is implicated in the preclinical, moderate, and late stages of AD ( Sung et al, 2020 ). In APP transgenic mice, Rd pretreatment at 10 mg/kg significantly suppresses the NF-κB pathway activity, reducing the generation of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and S100 calcium-binding protein B (S100β), which can improve learning and memory abilities ( Liu et al, 2015a ).…”