Modeling Alzheimer’s disease with iPSC-derived brain cells

Molecular Psychiatry, Journal Year: 2019, Volume and Issue: 25(1), P. 148 - 167

Published: Aug. 7, 2019

Alzheimer’s disease is a devastating neurodegenerative disorder with no cure. Countless promising therapeutics have shown efficacy in rodent models yet failed to benefit human patients. While hope remains that earlier intervention existing will improve outcomes, it becoming increasingly clear new approaches understand and combat the pathophysiology of are needed. Human induced pluripotent stem cell (iPSC) technologies changed face preclinical research iPSC-derived types being utilized study an array conditions, including disease. All major brain can now be differentiated from iPSCs, while complex co-culture systems developed facilitate neuroscience research. Many cellular functions perturbed recapitulated using cells vitro, platforms beginning yield insights into interactions occur between during neurodegeneration. Further, iPSC-based genome editing tools critical understanding roles numerous genes mutations found modify risk past decade. still their relative infancy, these developing hold considerable promise push forward efforts other disorders.

Language: Английский

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Mitochondria as Potential Targets in Alzheimer Disease Therapy: An Update

Frontiers in Pharmacology, Journal Year: 2019, Volume and Issue: 10

Published: Aug. 23, 2019

Alzheimer disease (AD) is a progressive and deleterious neurodegenerative disorder that affects mostly the elderly population. At moment, no effective treatments are available in market, making whole situation compelling challenge for societies worldwide. Recently, novel mechanisms have been proposed to explain etiology of this leading new concept AD multifactor pathology. Among others, function mitochondria has considered as one intracellular processes severely compromised since early stages likely represents common feature many diseases. Many mitochondrial parameters decline already during aging, reaching an extensive functional failure concomitant with onset conditions, although exact timeline these events still unclear. Thereby, it not surprising therapeutic targets diseases including AD. Together overview role dysfunction, review examines pros cons tested approaches targeting context Since therapies shown different degrees progress, imperative perform detailed analysis significance deterioration pharmacological treatment at level. This step would be very important field, drug missing concepts urgently needed.

Language: Английский

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Mediterranean diet and the hallmarks of ageing

European Journal of Clinical Nutrition, Journal Year: 2021, Volume and Issue: 75(8), P. 1176 - 1192

Published: Jan. 29, 2021

Language: Английский

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Oxidative stress and regeneration

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 181, P. 154 - 165

Published: Feb. 8, 2022

Language: Английский

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Influence of the Mediterranean Diet on Healthy Aging

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4491 - 4491

Published: Feb. 24, 2023

The life expectancy of the global population has increased. Aging is a natural physiological process that poses major challenges in an increasingly long-lived and frail population. Several molecular mechanisms are involved aging. Likewise, gut microbiota, which influenced by environmental factors such as diet, plays crucial role modulation these mechanisms. Mediterranean well components present it, offer some proof this. Achieving healthy aging should be focused on promotion lifestyle habits reduce development pathologies associated with aging, order to increase quality In this review we analyze influence diet pathways microbiota more favorable patterns, its possible anti-aging treatment.

Language: Английский

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Mitochondria in Alzheimer’s Disease Pathogenesis

Life, Journal Year: 2024, Volume and Issue: 14(2), P. 196 - 196

Published: Jan. 30, 2024

Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years above. It causes dementia with memory loss deterioration in thinking language skills. AD characterized by specific pathology resulting from the accumulation brain of extracellular plaques amyloid-β intracellular tangles phosphorylated tau. The importance mitochondrial dysfunction pathogenesis, while previously underrecognized, now more appreciated. Mitochondria are an essential organelle involved cellular bioenergetics signaling pathways. Mitochondrial processes crucial for synaptic activity such as mitophagy, trafficking, fission, fusion dysregulated brain. Excess fission fragmentation yield mitochondria low energy production. Reduced glucose metabolism also observed hypometabolic state, particularly temporo-parietal regions. This review addresses multiple ways which abnormal structure function contribute to AD. Disruption electron transport chain ATP production neurotoxic because cells have disproportionately high demands. In addition, oxidative stress, extremely damaging nerve cells, rises dramatically dyshomeostasis. Restoring health may be viable approach treatment.

Language: Английский

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Magnesium and the Hallmarks of Aging

Nutrients, Journal Year: 2024, Volume and Issue: 16(4), P. 496 - 496

Published: Feb. 9, 2024

Magnesium is an essential ion in the human body that regulates numerous physiological and pathological processes. deficiency very common old age. Age-related chronic diseases aging process itself are frequently associated with low-grade inflammation, called ‘inflammaging’. Because magnesium insufficiency has been linked to excessive generation of inflammatory markers free radicals, inducing a state, we formerly hypothesized inadequacy may be considered among intermediaries helping us explain link between inflammaging aging-associated diseases. We show this review evidence relationship all hallmarks (genomic instability, telomere attrition, epigenetic alterations, loss proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, disabled autophagy, dysbiosis, inflammation), which positively affect healthspan. It feasible hypothesize maintaining optimal balance during one’s life course turn out safe economical strategy contributing promotion healthy aging. Future well-designed studies necessary further explore hypothesis.

Language: Английский

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MicroRNAs: pioneering regulators in Alzheimer’s disease pathogenesis, diagnosis, and therapy

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 10, 2024

Language: Английский

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A review on fly ash from coal-fired power plants: chemical composition, regulations, and health evidence

Reviews on Environmental Health, Journal Year: 2020, Volume and Issue: 35(4), P. 401 - 418

Published: April 22, 2020

Abstract Throughout the world, coal is responsible for generating approximately 38% of power. Coal ash, a waste product, generated from combustion coal, consists fly bottom boiler slag, and flue gas desulfurization material. Fly which main component composed spherical particulate matter with diameters that range 0.1 μm to >100 μm. ash predominately silica, aluminum, iron, calcium, oxygen, but particles may also contain heavy metals such as arsenic lead at trace levels. Most nations throughout world do not consider hazardous therefore regulations on its disposal storage are lacking. beneficially reused in products concrete stored landfills surface impoundments. Fugitive dust emissions leaching into groundwater impoundments put people risk exposure. There limited epidemiological studies regarding health effects In this article, authors provide an overview chemical composition, greatest amount evidence impacts associated exposure ash.

Language: Английский

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Amyloid-β42/40 ratio drives tau pathology in 3D human neural cell culture models of Alzheimer’s disease

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: March 13, 2020

Abstract The relationship between amyloid-β (Aβ) species and tau pathology in Alzheimer’s disease (AD) is not fully understood. Here, we provide direct evidence that Aβ42/40 ratio, total Aβ level, plays a critical role inducing neurofibrillary tangles (NTFs) human neurons. Using 3D-differentiated clonal neural progenitor cells (hNPCs) expressing varying levels of amyloid β precursor protein (APP) presenilin 1 (PS1) with AD mutations, show pathogenic accumulation aggregation are tightly correlated ratio. Roles ratio on also confirmed APP transmembrane domain (TMD) mutant hNPCs, which display differential ratios without PS1. Moreover, naïve hNPCs co-cultured TMD I45F (high Aβ42/40) cells, I47F (low Aβ42/40), develop robust 3D non-cell autonomous cell culture system. These results emphasize the importance reducing therapy.

Language: Английский

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