The role of innate immune responses and neuroinflammation in amyloid accumulation and progression of Alzheimer's disease

Abstract

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The Role of Macrophage Migration Inhibitory Factor in Alzheimer′s Disease: Conventionally Pathogenetic or Unconventionally Protective?

“…It is proposed that during the development of AD misfolded and aggregated proteins might act as DAMP that binds pathogen PRR including class A scavenger receptor A1, CD36, CD14, α6β1 integrin, CD47, and toll like receptors expressed by microglial cells and astrocytes. This would in turn determine the release of inflammatory mediators such as NO and ROS, as well as proinflammatory cytokines, including TNF-α and IL-1β [13][14][15][16].…”

“…It has therefore been proposed that pro-inflammatory cytokines may contribute to AD pathogenesis through multiple pathways, including the induction of indoleamine 2,3-dioxygenase that increases the levels of the quinolinic acid, a neurotoxic factor, and in turn promotes tau hyperphosphorylation [13][14][15][16]. The role of anti-inflammatory cytokines, primarily belonging to the Th2 and Th3 cell subsets in the process of AD, is also worth mentioning as they might exert protective effects against AD by counteracting the effects of pro-inflammatory cytokines [13][14][15][16].…”

“…It has therefore been proposed that pro-inflammatory cytokines may contribute to AD pathogenesis through multiple pathways, including the induction of indoleamine 2,3-dioxygenase that increases the levels of the quinolinic acid, a neurotoxic factor, and in turn promotes tau hyperphosphorylation [13][14][15][16]. The role of anti-inflammatory cytokines, primarily belonging to the Th2 and Th3 cell subsets in the process of AD, is also worth mentioning as they might exert protective effects against AD by counteracting the effects of pro-inflammatory cytokines [13][14][15][16]. For example, transforming growth factor (TGF)-β that is a prototypical anti-inflammatory cytokine produced by Th3 cells is capable of ameliorating Aβ-induced cytotoxicity, in vivo and in vitro, and deficiency of TGF-β1 promotes both Aβ accumulation and NFTs formation [13][14][15][16].…”

“…The role of anti-inflammatory cytokines, primarily belonging to the Th2 and Th3 cell subsets in the process of AD, is also worth mentioning as they might exert protective effects against AD by counteracting the effects of pro-inflammatory cytokines [13][14][15][16]. For example, transforming growth factor (TGF)-β that is a prototypical anti-inflammatory cytokine produced by Th3 cells is capable of ameliorating Aβ-induced cytotoxicity, in vivo and in vitro, and deficiency of TGF-β1 promotes both Aβ accumulation and NFTs formation [13][14][15][16]. This pathogenetic hypothesis is also consistent with the epidemiologic evidence indicating an affirmative influence of non-steroidal anti-inflammatory drugs (NSAIDs) on delaying the progression of AD and have suggested that a blockade of the ongoing inflammatory processes may delay the progression AD [1].…”

“…It is important to note that despite local recruitment of brain microglia to the sites of amyloid deposition, they ultimately fail in preventing the formation of β-amyloid plaques [13][14][15][16].…”