Role of reactive oxygen species in the progression of Alzheimer’s disease

Drug Discovery Today, Journal Year: 2020, Volume and Issue: 26(3), P. 794 - 803

Published: Dec. 8, 2020

Language: Английский

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Oxidative stress and altered mitochondrial protein expression in the absence of amyloid-β and tau pathology in iPSC-derived neurons from sporadic Alzheimer's disease patients

Stem Cell Research, Journal Year: 2018, Volume and Issue: 27, P. 121 - 130

Published: Jan. 28, 2018

Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD) and increased production reactive oxygen species (ROS) has been described in postmortem brain samples animal models. However, these observations were made at late stage the inability to examine an early, presymptomatic phase human neurons impeded our understanding cause or consequence mitochondrial AD. We used induced pluripotent stem cell-derived neuronal cells (iN cells) from sporadic AD (SAD) patients healthy control subjects (HCS) show aberrant function patient-derived cells. observed that cultures some produced more ROS displayed higher levels DNA damage. Furthermore, showed oxidative phosphorylation chain complexes, whereas fission fusion proteins not affected. Surprisingly, effects neither correlated with Aβ nor phosphorylated total tau levels. Synaptic protein also unaffected SAD iN The results this study give new insights into constitutional metabolic changes prone develop pathology. They suggest may have integral role development prior appearance amyloid

Language: Английский

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Therapeutic Strategies Targeting Amyloid-β in Alzheimer’s Disease

Current Alzheimer Research, Journal Year: 2019, Volume and Issue: 16(5), P. 418 - 452

Published: March 25, 2019

Alzheimer's disease (AD) is a neurodegenerative disorder linked to protein misfolding and aggregation. AD pathologically characterized by senile plaques formed extracellular Amyloid-β (Aβ) peptide Intracellular Neurofibrillary Tangles (NFT) hyperphosphorylated tau protein. Extensive synaptic loss neuronal degeneration are responsible for memory impairment, cognitive decline behavioral dysfunctions typical of AD. Amyloidosis has been implicated in the depression acetylcholine synthesis release, overactivation N-methyl-D-aspartate (NMDA) receptors increased intracellular calcium levels that result excitotoxic degeneration. Current drugs used treatment either cholinesterase inhibitors or NMDA receptor antagonists; however, they provide only symptomatic relief do not alter progression disease. Aβ product Amyloid Precursor Protein (APP) processing after successive cleavage β- γ-secretases while APP proteolysis α-secretase results non-amyloidogenic products. According amyloid cascade hypothesis, dyshomeostasis accumulation aggregation into soluble oligomers insoluble fibrils. The former synaptotoxic can induce hyperphosphorylation latter deposit elicit proinflammatory responses, contributing oxidative stress, neuroinflammation. Aβ-protein-targeted therapeutic strategies thus promising disease-modifying approach prevention This review summarizes recent findings on Aβ-protein targeted drugs, including β-secretase inhibitors, γ-secretase modulators, activators, direct immunotherapy targeting Aβ, focusing mainly those currently under clinical trials.

Language: Английский

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Plasmalogens and Chronic Inflammatory Diseases

Frontiers in Physiology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 21, 2021

It is becoming widely acknowledged that lipids play key roles in cellular function, regulating a variety of biological processes. Lately, subclass glycerophospholipids, namely plasmalogens, has received increased attention due to their association with several degenerative and metabolic disorders as well aging. All these pathophysiological conditions involve chronic inflammatory processes, which have been linked decreased levels plasmalogens. Currently, there lack full understanding the molecular mechanisms governing plasmalogens inflammation. However, it shown could trigger either an anti- or pro-inflammation response. While anti-inflammatory response seems be entire plasmalogen molecule, its pro-inflammatory associated hydrolysis, i.e ., release arachidonic acid, which, turn, serves precursor produce lipid mediators. Moreover, comprise large fraction total humans, changes change membrane properties and, therefore, signaling pathways involved cascade. Restoring by use replacement therapy successful strategy ameliorating pathological hallmarks diseases. The purpose this review highlight emerging role promising treatment pathologies.

Language: Английский

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The interplay among oxidative stress, brain insulin resistance and AMPK dysfunction contribute to neurodegeneration in type 2 diabetes and Alzheimer disease

Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 176, P. 16 - 33

Published: Sept. 14, 2021

Language: Английский

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