Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease

Current Neuropharmacology, Journal Year: 2020, Volume and Issue: 18(11), P. 1106 - 1125

Published: May 28, 2020

The only conclusive way to diagnose Alzheimer's is carry out brain autopsy of the patient's tissue and ascertain whether subject had or any other form dementia. However, due non-feasibility such methods, conclude conditions, medical practitioners use tests that examine a mental ability.Accurate diagnosis at an early stage need hour for initiation therapy. cause most cases still remains unknown except where genetic distinctions have been observed. Thus, standard drug regimen ensues in every patient, irrespective cause, which may not always be beneficial halting reversing disease progression. To provide better life patients by suppressing existing symptoms, diagnosis, curative therapy, site-specific delivery drugs, application hyphenated methods like artificial intelligence brought into main field therapeutics.In this review, we compiled hypotheses explain disease, highlighted gene immunotherapy, peptidomimetics, metal chelators, probiotics quantum dots as advancements strategies manage Alzheimer's.Biomarkers, brain-imaging, theranostics, along with intelligence, are understood future management Alzheimer's.

Language: Английский

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Black Phosphorus Nanosheets as a Neuroprotective Nanomedicine for Neurodegenerative Disorder Therapy

Advanced Materials, Journal Year: 2017, Volume and Issue: 30(3)

Published: Nov. 30, 2017

Transition-metal dyshomeostasis is recognized as a critical pathogenic factor at the onset and progression of neurodegenerative disorder (ND). Excess transition-metal ions such Cu2+ can catalyze generation cytotoxic reactive oxygen species thereafter induce neuronal cell apoptosis. Exploring new chelating agents, which are not only capable capturing excess redox-active metal, but also cross blood-brain barrier (BBB), highly desired for ND therapy. Herein, it demonstrated that 2D black phosphorus (BP) nanosheets capture efficiently selectively to protect cells from -induced neurotoxicity. Moreover, both in vitro vivo studies show BBB permeability BP significantly improved under near-infrared laser irradiation due their strong photothermal effect, overcomes drawback conventional agents. Furthermore, excellent biocompatibility stability guarantee biosafety future clinical applications. Therefore, these features make have great potential work an efficient neuroprotective nanodrug

Language: Английский

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Metal Ions in Alzheimer’s Disease: A Key Role or Not?

Accounts of Chemical Research, Journal Year: 2019, Volume and Issue: 52(7), P. 2026 - 2035

Published: July 5, 2019

Despite tremendous research efforts in universities and pharmaceutical companies, effective drugs are still lacking for the treatment of Alzheimer's disease (AD). The biochemical mechanisms this devastating neurodegenerative have not yet been clearly understood. Besides a small percentage cases with early onset having genetic origin (<5%, familial AD), most develop elderly as sporadic form due to multiple complex parameters aging. Consequently, AD is spreading all countries long life expectancy. characterized by deposition senile plaques made β-amyloid proteins (Aβ) hyperphosphorylation tau proteins, which considered main drug targets up now. However, antibodies targeting amyloid aggregates, well enzyme inhibitors aiming modify precursor protein processing, failed improve cognition clinical trials. Thus, set drugs, it urgent enlarge panel targets. Evidence link between redox metal dysregulation has also supported post-mortem analyses plaques, revealed accumulation copper, iron, zinc 5.7, 2.8, 3.1 times, respectively, levels observed normal brains. Copper-amyloid complexes, presence endogenous reductants, able catalyze reduction dioxygen produce reduced, reactive oxygen species (ROS), leading neuron death. possibility using chelators regenerate trafficking ions promising strategy order reduce stress lethal neurons. attempts use therapeutic agents limited existing molecules available from shelves. Very few resulted rational design create safety profile cross blood-brain barrier after an oral administration. In human body, metals handled sophisticated network strictly control their transport reactivity. Abnormal concentrations certain may lead pathological events misaccumulation irregular restore homeostasis should carefully take into account coordination chemistry specificities concerned redox-active ions. This Account focused on role biologically transition metals, iron copper. For recent debate possible magnetite pathogenesis presented. section devoted copper specific candidates regulate oxidative damage responsible death A short survey non-redox-active included at beginning, such aluminum its controversial key ion brain.

Language: Английский

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Current Research Therapeutic Strategies for Alzheimer’s Disease Treatment

Neural Plasticity, Journal Year: 2016, Volume and Issue: 2016, P. 1 - 15

Published: Jan. 1, 2016

Alzheimer’s disease (AD) currently presents one of the biggest healthcare issues in developed countries. There is no effective treatment capable slowing down progression. In recent years main focus research on novel pharmacotherapies was based amyloidogenic hypothesis AD, which posits that beta amyloid (A β ) peptide chiefly responsible for cognitive impairment and neuronal death. The goal such treatments (a) to reduce A production through inhibition γ secretase enzymes (b) promote dissolution existing cerebral plaques. However, this approach has proven be only modestly effective. Recent studies suggest an alternative strategy centred downstream signalling, particularly at synapse. oligomers may cause aberrant N-methyl-D-aspartate receptor (NMDAR) activation postsynaptically by forming complexes with cell-surface prion protein (PrPC). PrPC enriched postsynaptic density, where it interacts Fyn tyrosine kinase. occurs when bound PrPC-Fyn complex. causes phosphorylation NR2B subunit metabotropic glutamate 5 (mGluR5). kinase blockers masitinib saracatinib have efficacious treating AD symptoms experimental mouse models disease.

Language: Английский

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Copper toxicology, oxidative stress and inflammation using zebrafish as experimental model

Journal of Applied Toxicology, Journal Year: 2016, Volume and Issue: 36(7), P. 876 - 885

Published: Feb. 17, 2016

Abstract Copper is an essential micronutrient and a key catalytic cofactor in wide range of enzymes. As trace element, copper levels are tightly regulated both its deficit excess deleterious to the organism. Under inflammatory conditions, serum increased trigger oxidative stress responses that activate responses. Interestingly, dyshomeostasis, inflammation commonly present several chronic diseases. exposure can be easily modeled zebrafish; consolidated model toxicology with increasing interest immunity‐related research. result developmental, economical genetic advantages, this freshwater teleost uniquely suitable for chemical large‐scale screenings, representing powerful experimental tool whole‐organism approach, mechanistic studies, disease modeling beyond. toxicological more recently pro‐inflammatory effects have been investigated larval adult zebrafish breakthrough findings. Here, we provide overview metabolism health on models. Copper‐induced highlighted owing potential mimic pro‐oxidative features combined tractability could help further understanding metabolism, related Copyright © 2016 John Wiley & Sons, Ltd.

Language: Английский

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Iron Homeostasis Disorder and Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(22), P. 12442 - 12442

Published: Nov. 18, 2021

Iron is an essential trace metal for almost all organisms, including human; however, oxidative stress can easily be caused when iron in excess, producing toxicity to the human body due its capability both electron donor and acceptor. Although there a strict regulation mechanism homeostasis brain, it usually inevitably disturbed by genetic environmental factors, or disordered with aging, which leads metabolism diseases, many neurodegenerative diseases such as Alzheimer’s disease (AD). AD one of most common degenerative central nervous system (CNS) threatening health. However, precise pathogenesis still unclear, seriously restricts design interventions treatment drugs based on AD. Many studies have observed abnormal accumulation different regions resulting cognitive, memory, motor other nerve damages. Understanding metabolic balance brain crucial AD, would provide new cures disease. This paper reviews recent progress relationship between from aspects absorption intestinal cells, storage cells organs, especially prospects future directions treatments.

Language: Английский

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The metal ion hypothesis of Alzheimer’s disease and the anti-neuroinflammatory effect of metal chelators

Bioorganic Chemistry, Journal Year: 2022, Volume and Issue: 131, P. 106301 - 106301

Published: Nov. 25, 2022

Language: Английский

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Metallobiology and therapeutic chelation of biometals (copper, zinc and iron) in Alzheimer’s disease: Limitations, and current and future perspectives

Journal of Trace Elements in Medicine and Biology, Journal Year: 2021, Volume and Issue: 67, P. 126779 - 126779

Published: May 15, 2021

Alzheimer's disease (AD) is the most prevalent cause of cognitive impairment and dementia worldwide. The pathobiology has been studied in form several hypotheses, ranging from oxidative stress, amyloid-beta (Aβ) aggregation, accumulation tau forming neurofibrillary tangles (NFT) through metal dysregulation homeostasis, dysfunction cholinergic system, to inflammatory autophagic mechanism. However, none these hypotheses led confirmed diagnostics or approved cure for disease. This review aimed as a basic an encyclopedic short course into metals AD discusses advances chelation strategies developments adopted treatment Since there accumulating evidence role both biometal dyshomeostasis (iron (Fe), copper (Cu), zinc (Zn)) metal-amyloid interactions that lead pathogenesis AD, this focuses on unraveling therapeutic have considered disease, aiming sequester free protein-bound ions reducing cerebral burden. Promising compounds possessing chemically modified moieties evolving multi-target ligands used anti-AD drug candidates are also covered. Several multidirectional multifaceted studies therapeutics show need improved synthesis, screening, analysis be able effectively present chelating drugs. Most limitations their physicochemical properties; some enhance redistribution ions, while others indirectly activate signaling pathways AD. process vivo still needs established design potential bi-functionally well inhibit Aβ aggregation by competing with metal-induced damage neurotoxicity may signal bright end chelation-based

Language: Английский

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The cellular model for Alzheimer's disease research: PC12 cells

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Jan. 4, 2023

Alzheimer's disease (AD) is a common age-related neurodegenerative characterized by progressive cognitive decline and irreversible memory impairment. Currently, several studies have failed to fully elucidate AD's cellular molecular mechanisms. For this purpose, research on related models may propose potential predictive for the drug development of AD. Therefore, many cells neuronal properties are widely used mimic pathological process AD, such as PC12, SH-SY5Y, N2a, especially PC12 pheochromocytoma cell line. Thus, review covers most systematic essay that study We depict source, culture condition, differentiation methods, transfection drugs inducing general approaches (evaluation methods metrics), in vitro parallel with cells.

Language: Английский

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Halophytes: Gourmet food with nutritional health benefits?

Journal of Food Composition and Analysis, Journal Year: 2017, Volume and Issue: 59, P. 35 - 42

Published: Feb. 6, 2017

Language: Английский

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