New Insights into the Development of Donepezil-Based Hybrid and Natural Molecules as Multi-Target Drug Agents for Alzheimer’s Disease Treatment DOI Creative Commons
Violina T. Angelova, Boris Petrov Stoyanov, Rumyana Simeonova

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(22), P. 5314 - 5314

Published: Nov. 11, 2024

Alzheimer's disease (AD) involves a complex pathophysiology with multiple interconnected subpathologies, including protein aggregation, impaired neurotransmission, oxidative stress, and microglia-mediated neuroinflammation. Current treatments, which generally target single subpathology, have failed to modify the disease's progression, providing only temporary symptom relief. Multi-target drugs (MTDs) address several aggregation of pathological proteins. In this review, we cover hybrid molecules published between 2014 2024. We offer an overview strategies employed in drug design approaches that led notable improvements reduced hepatotoxicity. Our aim is insights into potential development new drugs. This highlights multi-target featuring heterocycles

Language: Английский

Peripheral proteinopathy in neurodegenerative diseases DOI Creative Commons
Bin Xu, Lei Xia, Ying Yang

et al.

Translational Neurodegeneration, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 16, 2025

Proteinopathies in neurology typically refer to pathological changes proteins associated with neurological diseases, such as the aggregation of amyloid β and Tau Alzheimer's disease, α-synuclein Parkinson's disease multiple system atrophy, TAR DNA-binding protein 43 amyotrophic lateral sclerosis frontotemporal dementia. Interestingly, these are also commonly found peripheral tissues, raising important questions about their roles disorders. Multiple studies have shown that peripherally derived not only travel brain through various routes, aggravating pathology, but contribute significantly dysfunction, highlighting crucial impact on diseases. Investigating how influence progression disorders could open new horizons for achieving early diagnosis treatment. This review summarizes distribution, transportation pathways, pathogenic mechanisms several neurodegenerative disease-related periphery, proposing targeting be a promising strategy preventing managing

Language: Английский

Citations

0
Krüppel-like factor 9 alleviates Alzheimer’s disease via IDE-mediated Aβ degradation DOI

Yue-yao Feng,

Jianwei Hao, Yujie Zhang

et al.

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Language: Английский

Citations

0
Cellular Prion Protein and Amyloid-β Oligomers in Alzheimer’s Disease—Are There Connections? DOI Open Access
Michał Fułek, Naomi Hachiya, Martyna Gachowska

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2097 - 2097

Published: Feb. 27, 2025

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Pathological deposits neurotoxin proteins within brain, such as amyloid-β and hyperphosphorylated tau tangles, are prominent features in AD. The prion protein (PrP) involved neurodegeneration via its conversion from normal cellular form (PrPC) to infection scrapie (PrPSc) form. Some studies indicated that post-translationally modified PrPC isoforms play a fundamental role AD pathological progression. Several have shown interaction Aβ oligomers (Aβos) with N-terminal residues region appears critical for neuronal toxicity. PrPC-Aβ binding always occurs brains never detected non-demented controls, aggregates restricted N-terminus PrPC. In this study, we aimed gather all recent information about connections between AD, potential clinical implications.

Language: Английский

Citations

0
Inhibitory Effects of Gliadin Hydrolysates on BACE1 Expression and APP Processing to Prevent Aβ Aggregation DOI Open Access
Chin‐Yu Lin,

Cheng-Hong Hsieh,

Paul B.S. Lai

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 13212 - 13212

Published: Dec. 9, 2024

Alzheimer's disease (AD), a leading neurodegenerative disorder, is closely associated with the accumulation of amyloid-beta (Aβ) peptides in brain. The enzyme β-secretase (BACE1), pivotal Aβ production, represents promising therapeutic target for AD. While bioactive derived from food protein hydrolysates have neuroprotective properties, their inhibitory effects on BACE1 remain largely unexplored. In this study, we evaluated potential gliadin, whey, and casein proteins prepared using bromelain, papain, thermolysin. Through vitro cellular assays, bromelain-hydrolyzed gliadin (G-Bro) emerged as most potent inhibitor, an IC

Language: Английский

Citations

1
New Insights into the Development of Donepezil-Based Hybrid and Natural Molecules as Multi-Target Drug Agents for Alzheimer’s Disease Treatment DOI Creative Commons
Violina T. Angelova, Boris Petrov Stoyanov, Rumyana Simeonova

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(22), P. 5314 - 5314

Published: Nov. 11, 2024

Alzheimer's disease (AD) involves a complex pathophysiology with multiple interconnected subpathologies, including protein aggregation, impaired neurotransmission, oxidative stress, and microglia-mediated neuroinflammation. Current treatments, which generally target single subpathology, have failed to modify the disease's progression, providing only temporary symptom relief. Multi-target drugs (MTDs) address several aggregation of pathological proteins. In this review, we cover hybrid molecules published between 2014 2024. We offer an overview strategies employed in drug design approaches that led notable improvements reduced hepatotoxicity. Our aim is insights into potential development new drugs. This highlights multi-target featuring heterocycles

Language: Английский

Citations

0