Abstract:Alzheimer's disease (AD) is the most common (60% to 80%) age-related disease associated with dementia and is characterized by a deterioration of behavioral and cognitive capacities leading to death in few years after diagnosis, mainly due to complications from chronic illness. The characteristic hallmarks of the disease are extracellular senile plaques (SPs) and intracellular neurofibrillary tangles (NFTs) with neuropil threads, which are a direct result of amyloid precursor protein (APP) processing to Aβ, and… Show more
“…Alternative processing of APP by α-secretase generates soluble APPα that has neurotrophic and neuroprotective properties. Calpain is a Ca2+-dependent protease which activity is dysregulated in AD, causing an increase of BACE1 expression, tau phosphorylation, oxidative stress and other excitotoxicity assaults ( Mahaman et al, 2019 ).…”
Fatty acids play a crucial role in the brain as specific receptor ligands and as precursors of bioactive metabolites. Conjugated linoleic acid (CLA), a group of positional and geometric isomers of linoleic acid (LA, 18:2 n-6) present in meat and dairy products of ruminants and synthesized endogenously in non-ruminants and humans, has been shown to possess different nutritional properties associated with health benefits. Its ability to bind to peroxisome proliferator-activated receptor (PPAR) α, a nuclear receptor key regulator of fatty acid metabolism and inflammatory responses, partly mediates these beneficial effects. CLA is incorporated and metabolized into brain tissue where induces the biosynthesis of endogenous PPARα ligands palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), likely through a positive feedback mechanism where PPARα activation sustains its own cellular effects through ligand biosynthesis. In addition to PPARα, PEA and OEA may as well bind to other receptors such as TRPV1, further extending CLA own anti-neuroinflammatory actions. Future studies are needed to investigate whether dietary CLA may exert anti-inflammatory activity, particularly in the setting of neurodegenerative diseases and neuropsychiatric disorders with a neuroinflammatory basis.
“…Alternative processing of APP by α-secretase generates soluble APPα that has neurotrophic and neuroprotective properties. Calpain is a Ca2+-dependent protease which activity is dysregulated in AD, causing an increase of BACE1 expression, tau phosphorylation, oxidative stress and other excitotoxicity assaults ( Mahaman et al, 2019 ).…”
Fatty acids play a crucial role in the brain as specific receptor ligands and as precursors of bioactive metabolites. Conjugated linoleic acid (CLA), a group of positional and geometric isomers of linoleic acid (LA, 18:2 n-6) present in meat and dairy products of ruminants and synthesized endogenously in non-ruminants and humans, has been shown to possess different nutritional properties associated with health benefits. Its ability to bind to peroxisome proliferator-activated receptor (PPAR) α, a nuclear receptor key regulator of fatty acid metabolism and inflammatory responses, partly mediates these beneficial effects. CLA is incorporated and metabolized into brain tissue where induces the biosynthesis of endogenous PPARα ligands palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), likely through a positive feedback mechanism where PPARα activation sustains its own cellular effects through ligand biosynthesis. In addition to PPARα, PEA and OEA may as well bind to other receptors such as TRPV1, further extending CLA own anti-neuroinflammatory actions. Future studies are needed to investigate whether dietary CLA may exert anti-inflammatory activity, particularly in the setting of neurodegenerative diseases and neuropsychiatric disorders with a neuroinflammatory basis.
“…Calcium unbalance may lead to activation of calcium-dependent proteases, calpains, which are implicated in the granular disintegration of the axonal cytoskeleton, a hallmark of Wallerian degeneration. Indeed, calpains are abnormally activated in AD brains, and they have been implicated in the development of tau pathology (Mahaman et al, 2019).…”
Section: The Role Of Tau-mediated Axonal Transport Disruption In Axonmentioning
Alzheimer's disease (AD) represents the most common age-related neurodegenerative disorder, affecting around 35 million people worldwide. Despite enormous efforts dedicated to AD research over decades, there is still no cure for the disease. Misfolding and accumulation of Aβ and tau proteins in the brain constitute a defining signature of AD neuropathology, and mounting evidence has documented a link between aggregation of these proteins and neuronal dysfunction. In this context, progressive axonal degeneration has been associated with early stages of AD and linked to Aβ and tau accumulation. As the axonal degeneration mechanism has been starting to be unveiled, it constitutes a promising target for neuroprotection in AD. A comprehensive understanding of the mechanism of axonal destruction in neurodegenerative conditions is therefore critical for the development of new therapies aimed to prevent axonal loss before irreversible neuronal death occurs in AD. Here, we review current evidence of the involvement of Aβ and tau pathologies in the activation of signaling cascades that can promote axonal demise.
“…Alzheimer's disease is a progressive neurological disorder that is characterized by memory loss and confusion. There is good evidence indicating that the abnormal deposition of β‐amyloid (Aβ) is a primary cause of the pathogenesis of Alzheimer's disease . Wang et al synthesized 19 (Figure ).…”
Section: Applications Of Aie Probes In the Field Of Biological Sciencementioning
confidence: 99%
“…There is good evidence indicating that the abnormal deposition of β-amyloid (Aβ) is a primary cause of the pathogenesis of Alzheimer's disease. 118,119 Wang et al 120 synthesized 19 (Figure 2). It has AIE features to be used for detection and super-resolution imaging of fibrillar amyloid.…”
Section: Diagnosis Based Upon the Aie Imaging Of The Lesionmentioning
Fluorescence imaging is a promising visualization tool and possesses the advantages of in situ response and facile operation; thus, it is widely exploited for bioassays. However, traditional fluorophores suffer from concentration limits because they are always quenched when they aggregate, which impedes applications, especially for trace analysis and real‐time monitoring. Recently, novel molecules with aggregation‐induced emission (AIE) characteristics were developed to solve the problems encountered when using traditional organic dyes, because these new molecules exhibit weak or even no fluorescence when they are in free movement states but emit intensely upon the restriction of intramolecular motions. Inspired by the excellent performances of AIE molecules, a substantial number of AIE‐based probes have been designed, synthesized, and applied to various fields to fulfill diverse detection tasks. According to numerous experiments, AIE probes are more practical than traditional fluorescent probes, especially when used in bioassays. To bridge bioimaging and materials engineering, this review provides a comprehensive understanding of the development of AIE bioprobes. It begins with a summary of mechanisms of the AIE phenomenon. Then, the strategies to realize accurate detection using AIE probes are discussed. In addition, typical examples of AIE‐active materials applied in diagnosis, treatment, and nanocarrier tracking are presented. In addition, some challenges are put forward to inspire more ideas in the promising field of AIE‐active materials.
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