Review on anti-alzheimer drug development: approaches, challenges and perspectives

RSC Advances, Journal Year: 2024, Volume and Issue: 14(16), P. 11057 - 11088

Published: Jan. 1, 2024

Alzheimer has many crucial factors that should be considered in order to get better results from clinical trials. Benzimidazole and its isosteres represent significant scaffolds for designing potential multi-target anti-alzheimer molecules.

Language: Английский

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A case for seeking sex-specific treatments in Alzheimer’s disease

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Feb. 13, 2024

There is no satisfactory explanation for the sex-related differences in incidence of many diseases and this also true Alzheimer’s disease (AD), where females have a higher lifetime risk developing make up about two thirds AD patient population. The importance understanding cause(s) that account disproportionate distribution cannot be overestimated, likely to significant factor search therapeutic strategies will combat and, furthermore, potentially point sex-targeted approach treatment. This review considers literature context what known impact sex on processes targeted by drugs are clinical trial AD, existing knowledge differing responses males these drugs. Current strongly supports view trials should assessing difference priority with focus exploring sex-stratified treatments.

Language: Английский

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Neuroprotective potential of hispidulin and diosmin: a review of molecular mechanisms

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(5)

Published: April 21, 2025

Language: Английский

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Pharmacochemical Strategies and Advances in Alzheimer's Disease Drug Development

Highlights in Science Engineering and Technology, Journal Year: 2025, Volume and Issue: 139, P. 283 - 293

Published: April 28, 2025

Alzheimer's disease (AD) is one of the diseases that seriously threaten human life and health. Currently, exact pathological mechanism still unknown, there are no drugs can terminate or reverse process, which have limited discovery AD-related targets development effectively treat AD. However, with deepening research on molecular computers artificial intelligence, some potential AD been discovered their structures analyzed, at same time, paradigm drug by chemical means has continuously expanded, provided medicinal chemists a variety methods strategies for designing new compounds thus synthesizing small molecules be effective in treating In this paper, we summarize four widely accepted hypotheses pathogenesis chemistry small-molecule development, based results recent years.

Language: Английский

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Secretase promotes AD progression: simultaneously cleave Notch and APP

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Nov. 20, 2024

Alzheimer's disease (AD) involves complex pathological mechanisms. Secretases include membrane protein extracellular structural domain proteases and intramembrane that cleave the topology to type I or II. can effectively regulate activation of Notch amyloid precursor (APP), key factors in progression AD cancer. This article systematically summarizes intracellular localization, cleavage sites products, biological functions six subtypes secretases (α-secretase, β-secretase, γ-secretase, δ-secretase, ε-secretase, η-secretase), for first time, elucidates commonalities differences between these secretases. We found each subtype secretase primarily cleaves APP as substrates, regulating Aβ levels through impact AD, while also cleaving receptors affect cancer progression. Finally, we review chemical structures, indications, research stages various inhibitors, emphasizing promising development inhibitors fields AD.

Language: Английский

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A Narrative Review on the Neuroprotective Potential of Brown Macroalgae in Alzheimer’s Disease

Nutrients, Journal Year: 2024, Volume and Issue: 16(24), P. 4394 - 4394

Published: Dec. 20, 2024

Systematic Alzheimer’s disease (AD) is a neurodegenerative increasingly prevalent in the aging population. AD characterized by pathological features such as β-amyloid (Aβ) plaque accumulation, tau neurofibrillary tangles formation, oxidative stress, an impaired cholinergic system, and neuroinflammation. Many therapeutic drugs have been developed to slow progression of targeting these mechanisms. However, synthetic drugs, donepezil memantine, can often lead side effects. In this context, seaweeds drawing attention nutrient source potential health-improving metabolites. Studies shown that extracts from brown macroalgae potentially reduce inflammation associated with diseases inhibiting proinflammatory cytokine expression. Furthermore, their bioactive compounds exhibit antioxidant properties vital combating stress. Antioxidants, mainly carotenoids phenolic compounds, linked improved cognitive function reduced risk disorders protecting neuronal cells through ability scavenge free radicals. addition, omega-3 fatty acids found certain support brain health function, further enhancing neuroprotective conclusion, review has comprehensively evaluated research conducted on last five years, covering methods obtaining against AD. The limited number clinical studies literature highlights need for research. This narrative provides basic framework new approaches strategies, those natural resources. they may play important role developing functional foods nutraceuticals human preventing managing diseases.

Language: Английский

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Five Key Criteria for Identifying Optimal Therapeutic Targets in Protein‐Mediated Diseases

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(4)

Published: Jan. 1, 2025

Abstract Therapeutic trends involve designing ligands to target proteins in various diseases, but no parallel filters have been established prioritize pathological within pathogens for optimal inhibition. This study unveils that order a protein serve as an therapeutic intervention, it must exhibit five key attributes. It should druggable site with recognized cleft which ligand can be fitted high specificity. possess unique structure, distinct sequences having low similarity other non‐targeted proteins. dispensable the pathogenesis of disease, and case microbial infection, crucial survival infectious organisms. available crystallized 3D structure enable high‐throughput screening candidate ligands. occupy accessible localization provide easy route reach its less effort. The justifies rules essential considering ideal any protein‐mediated dysfunction. When these targeting are found protein, eradicating intended ailment primarily enhanced time, money,

Language: Английский

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Application of the Trend of miRNA Expression Levels in APP/PS1 Mice Plasma for the Early Diagnosis of Alzheimer’s Disease

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Language: Английский

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Biotransformation of American Ginseng Stems and Leaves by an Endophytic Fungus Umbelopsis sp. and Its Effect on Alzheimer’s Disease Control

Nutrients, Journal Year: 2023, Volume and Issue: 15(23), P. 4878 - 4878

Published: Nov. 22, 2023

Common ginsenosides can be transformed into rare through microbial fermentation, and some prevent Alzheimer's disease (AD). This study aimed to transform common solid-state fermentation of American ginseng stems leaves (AGSL) by an endophytic fungus explore whether fermented saponin extracts AD. The powders AGSL were in a solid state fungus. Total saponins extracted from products using the methanol extraction method. types analyzed liquid chromatography mass spectrometry (LC/MS). Aβ42 concentration β-secretase activity measured ELISA for prevention After was NSJG, total extract G-SL higher than unfermented CK-SL. Rare ginsenoside Rh1 newly produced yield compound K (561.79%), Rh2 (77.48%), F2 (40.89%) increased G-SL. had inhibition rate on (42.75%) (42.22%) CK-SL, possibly because Rh1, Rh2, F2, included it have strong inhibitory effect show more effects AD may promising therapeutic drugs or nutrients

Language: Английский

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Effects and mechanisms of APP and its cleavage product Aβ in the comorbidity of sarcopenia and Alzheimer’s disease

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Nov. 25, 2024

Sarcopenia and AD are both classic degenerative diseases, there is growing epidemiological evidence of their comorbidity with aging; however, the mechanisms underlying biology commonality have not yet been thoroughly investigated. APP a membrane protein that expressed in tissues only nervous system but also NMJ muscle. Deposition its proteolytic cleavage product, Aβ, has described as central component pathogenesis. Recent studies shown excessive accumulation aberrant expression muscle lead to pathological lesions, pathogenic mechanism by which products act skeletal less well understood. By summarizing analyzing literature concerning role, pathogenicity muscles, we aimed explore intrinsic myocerebral comorbidities provide new perspectives theoretical foundations for prevention treatment sarcopenia comorbidities.

Language: Английский

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