Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 176, P. 16 - 33
Published: Sept. 14, 2021
Language: Английский
Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 176, P. 16 - 33
Published: Sept. 14, 2021
Language: Английский
Drug Discovery Today, Journal Year: 2020, Volume and Issue: 26(3), P. 794 - 803
Published: Dec. 8, 2020
Language: Английский
Citations
131Stem 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
Citations
119Current 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
Citations
117Frontiers 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
Citations
101Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 176, P. 16 - 33
Published: Sept. 14, 2021
Language: Английский
Citations
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