Prediction of Alzheimer’s disease-specific phospholipase c gamma-1 SNV by deep learning-based approach for high-throughput screening

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(3)

Published: Jan. 4, 2021

Exon splicing triggered by unpredicted genetic mutation can cause translational variations in neurodegenerative disorders. In this study, we discover Alzheimer's disease (AD)-specific single-nucleotide variants (SNVs) and abnormal exon of phospholipase c gamma-1 (

Language: Английский

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GENI as an AMPK Activator Binds α and γ Subunits and Improves the Memory Dysfunction of Alzheimer’s Disease Mouse Models via Autophagy and Neuroprotection

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 57 - 57

Published: Jan. 6, 2025

Geniposidic 4-isoamyl ester (GENI) with anti-aging effects is a new iridoid glycoside derivative from Gardenia jasminoides Ellis found in our previous study. In this study, to indicate whether compound has anti-Alzheimer’s disease (AD) effect, the galactose-induced AD mice and naturally aging were used do drug efficacy evaluation. Furthermore, Western blot, small interfering RNA (siRNA), affinity responsive target stability (DARTS), cellular thermal shift assay (CESTA), liquid chromatography-tandem mass spectrometry (LC/MS-MS), adenosine 5′-monophosphate-activated protein kinase (AMPK) mutants surface plasmon resonance (SPR) analysis utilized clarify mechanism of action identify molecule. GENI exerts anti-AD through neuroprotection modification autophagy neuron inflammation. Moreover, AMPK as produce an effect identified ASP148, ASP157, ASP166 α subunit lysine (LYS)148, aspartic acid (ASP)156, LYS309, ASP316 γ binding sites are confirmed. Meanwhile, AMPK/unc-51-like autophagy-activating 1 (ULK1)/microtubule-associated light chain 3 beta (LC3B) AMPK/mammalian rapamycin (mTOR) signaling pathways involved GENI. The findings provide perspective on treating neurodegenerative diseases by activating for energy metabolism disorder.

Language: Английский

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CRISPR/Cas9-Based therapeutics as a promising strategy for management of Alzheimer’s disease: progress and prospects

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: April 7, 2025

CRISPR/Cas9 technology has revolutionized genetic and biomedical research in recent years. It enables editing modulation of gene function with an unparalleled precision effectiveness. Among the various applications prospects this technology, opportunities it offers unraveling molecular underpinnings a myriad central nervous system diseases, including neurodegenerative disorders, psychiatric conditions, developmental abnormalities, are unprecedented. In review, we highlight CRISPR/Cas9-based therapeutics as promising strategy for management Alzheimer's disease transformative impact on AD research. Further, emphasize role generating accurate models identification novel therapeutic targets, besides CRISPR-based therapies aimed at correcting AD-associated mutations modulating processes. Furthermore, delivery systems reviewed potential non-viral nanotechnology-based carriers overcoming critical limitations effective is discussed. Overall, review highlights promise intricate processes underlying development AD, discusses its limitations, ethical concerns several challenges efficient across BBB, ensuring specificity, avoiding off-target effects. This article can be helpful better understanding based approaches way forward utilizing enormous targeted, gene-specific treatments that could change trajectory debilitating incurable illness.

Language: Английский

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An update on mammalian and non-mammalian animal models for biomarker development in neurodegenerative disorders

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: April 7, 2025

Neurodegeneration is one of the leading factor for death globally, affecting millions people. Developing animal models are critical to understand biological processes and comprehend pathological hallmarks neurodegenerative diseases. For decades, many have served as excellent tools determine disease progression, develop diagnostic methods design novel therapies against distinct pathologies. Here, we provide a comprehensive overview both, mammalian non-mammalian models, with focus on three most common aggressive disorders: Alzheimer's disease, Parkinson's Spinocerebellar ataxia-1. We highlight various approaches including transgene, gene transfer, chemically-induced used models. In particular, discuss applications both contributions in research neurodegeneration. It exciting learn roles pathomechanisms, identifying biomarkers hence devising interventions treat neuropathological conditions.

Language: Английский

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Reevaluating Alzheimer’s disease treatment: Can phytochemicals bridge the therapeutic Gap?

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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