Inflammation context in Alzheimer’s disease, a relationship intricate to define

Abstract

Alzheimer’s disease (AD), the most common form of dementia, is characterized by the accumulation of amyloid β (Aβ) and hyperphosphorylated tau protein aggregates. Importantly, Aβ and tau species are able to activate astrocytes and microglia, which release several proinflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β), together with reactive oxygen (ROS) and nitrogen species (RNS), triggering neuroinflammation. However, this inflammatory response has a dual function: it can play a protective role by increasing Aβ degradation and clearance, but it can also contribute to Aβ and tau overproduction and induce neurodegeneration and synaptic loss. Due to the significant role of inflammation in the pathogenesis of AD, several inflammatory mediators have been proposed as AD markers, such as TNF-α, IL-1β, Iba-1, GFAP, NF-κB, TLR2, and MHCII. Importantly, the use of anti-inflammatory drugs such as NSAIDs has emerged as a potential treatment against AD. Moreover, diseases related to systemic or local inflammation, including infections, cerebrovascular accidents, and obesity, have been proposed as risk factors for the development of AD. In the following review, we focus on key inflammatory processes associated with AD pathogenesis.

Therapeutic potential of aromatic plant extracts in Alzheimer's disease: Comprehensive review of their underlying mechanisms

“…Increasing evidence suggests that damaged neurons and deposits of insoluble Aβ peptides and neurofibrillary tangles are pathological triggers for neuroinflammation in AD. When these substances bind to the pattern recognition receptors of microglia and astrocytes, they induce transcriptional activation of downstream inflammatory response genes, thereby releasing inflammatory cytokines, the overproduction of which eventually leads to chronic neuroinflammation, thus exacerbating the pathogenesis of AD 33 . On the other hand, during peripheral inflammation, cytokines cross the BBB and cause brain microglia and astrocytes to react, further producing pro‐inflammatory mediators 34 .…”

“…When these substances bind to the pattern recognition receptors of microglia and astrocytes, they induce transcriptional activation of downstream inflammatory response genes, thereby releasing inflammatory cytokines, the overproduction of which eventually leads to chronic neuroinflammation, thus exacerbating the pathogenesis of AD. 33 On the other hand, during peripheral inflammation, cytokines cross the BBB and cause brain microglia and astrocytes to react, further producing pro-inflammatory mediators. 34 The production of inflammatory cytokines and mediators by microglia and astrocytes directly promotes the occurrence and development of AD.…”

“…Thymol(2-isopropyl-5-methylphenol) and carvacrol(5-isopropyl-2-methylphenol) are the main ingredients in the essential oils of numerous aromatic plants such as species of Zataria, Origanum, Thymbra, Thymus, Satureja, and Coridothymus of the family Lamiaceae and Lippia of Verbenaceae 18. Thymol or carvacrol may lightening cognitive impairment in rats received bilateral intrahippocampal injections of Aβ(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) 19. Among Aβrelated research items, the curcumin has received the most attention.Curcumin is a kind of phenolic compound obtained from the rhizome of some plants in the Zingiberaceae and Araneae families,20,21 which is the major constituent of the Asian spice.…”

Molecular Mechanisms of the Anti-Inflammatory Effects of Epigallocatechin 3-Gallate (EGCG) in LPS-Activated BV-2 Microglia Cells

“…Age-associated neurodegeneration alters these pathways’ typical function, leading to synaptic dysregulation, protein aggregation, blood–brain barrier disruption, chronic inflammation, and neuronal cell death. Nuclear Factor Kappa B (NF-κB) is a well-established transcription factor immunomodulator, aging controller, and mediator of inflammatory responses acting via proinflammatory cytokines, i.e., IL-6 and TNF-α [ 14 , 15 ]. The Phosphoinositide 3 Kinase/Protein Kinase B (PI3K-Akt) pathway modulates many microglial microenvironment cellular activities via its management of the mammalian mechanistic target of rapamycin (mTOR), which is a serine-threonine kinase involved in cellular metabolism, autophagy, aging, and nutrient regulation [ 16 ].…”

Assessing adipokines as potential biomarkers of dementia, Alzheimer's disease, and mild cognitive impairment: A systematic review and meta‐analysis

“…In turn, this response induces synaptic loss and neurodegeneration, and it further increases Aβ and tau levels, becoming a vicious cycle. 13 In this field, the study of adipokines might provide further light into the mechanisms linking alterations in body weight, inflammation, and neurodegeneration (Figure 1). The term adipokines refers to hundreds of different molecules that are secreted by the peripheral white adipose tissue and that exert their actions via autocrine, paracrine, or endocrine mechanisms, most of them in both the central (CNS) and the peripheral nervous systems.…”