Behavioural pharmacology predicts disrupted signalling pathways and candidate therapeutics from zebrafish mutants of Alzheimer’s disease risk genes DOI Open Access
François Kroll, Joshua Donnelly, Güliz Gürel Özcan

и другие.

Опубликована: Май 29, 2024

By exposing genes associated with disease, genomic studies provide hundreds of starting points that should lead to druggable processes. However, our ability systematically translate these findings into biological pathways remains limited. Here, we combine rapid loss-of-function mutagenesis Alzheimer’s risk and behavioural pharmacology in zebrafish predict disrupted processes candidate therapeutics. FramebyFrame, expanded package for the analysis larval behaviours, revealed decreased night-time sleep was common F0 knockouts all four late-onset tested. We developed an online tool, ZOLTAR, which compares any fingerprint a library fingerprints from larvae treated 3,674 compounds. ZOLTAR successfully predicted sorl1 mutants have serotonin signalling identified betamethasone as drug normalises excessive day-time presenilin-2 knockout minimal side effects. Predictive offers general framework rapidly link disease-associated pathways.

Язык: Английский

Unblinding in the lecanemab trial in Alzheimer’s disease DOI
Willem A. van Gool

Brain, Год журнала: 2023, Номер 146(11), С. e100 - e100

Опубликована: Май 18, 2023

Journal Article Unblinding in the lecanemab trial Alzheimer's disease Get access Willem A Van Gool Department of Public and Occupational Health, Amsterdam University Medical Centre, Amsterdam, The Netherlands Correspondence to: A. UMC Locatie AMC—Public Meibergdreef 9 1105 AZ, E-mail: [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Brain, Volume 146, Issue 11, November 2023, Page e100, https://doi.org/10.1093/brain/awad171 Published: 18 May 2023 history Received: 24 April Accepted: 13 Corrected typeset: 23 August

Язык: Английский

Процитировано

11
Behavioural pharmacology predicts disrupted signalling pathways and candidate therapeutics from zebrafish mutants of Alzheimer’s disease risk genes DOI Open Access
François Kroll, Joshua Donnelly, Güliz Gürel Özcan

и другие.

Опубликована: Янв. 14, 2025

By exposing genes associated with disease, genomic studies provide hundreds of starting points that should lead to druggable processes. However, our ability systematically translate these findings into biological pathways remains limited. Here, we combine rapid loss-of-function mutagenesis Alzheimer’s risk and behavioural pharmacology in zebrafish predict disrupted processes candidate therapeutics. FramebyFrame, expanded package for the analysis larval behaviours, revealed decreased night-time sleep was common F0 knockouts all four late-onset tested. We developed an online tool, ZOLTAR, which compares any fingerprint a library fingerprints from larvae treated 3,677 compounds. ZOLTAR successfully predicted sorl1 mutants have serotonin signalling identified betamethasone as drug normalises excessive day-time presenilin-2 knockout minimal side effects. Predictive offers general framework rapidly link disease-associated pathways.

Язык: Английский

Процитировано

0
Optimizing ResNet50 Performance Using Stochastic Gradient Descent on MRI Images for Alzheimer's Disease Classification DOI Creative Commons
Mohamed Amine Mahjoubi, Driss Lamrani, Shawki Saleh

и другие.

Intelligence-Based Medicine, Год журнала: 2025, Номер 11, С. 100219 - 100219

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Behavioural pharmacology predicts disrupted signalling pathways and candidate therapeutics from zebrafish mutants of Alzheimer’s disease risk genes DOI Creative Commons
François Kroll, Joshua Donnelly, Güliz Gürel Özcan

и другие.

eLife, Год журнала: 2025, Номер 13

Опубликована: Янв. 27, 2025

By exposing genes associated with disease, genomic studies provide hundreds of starting points that should lead to druggable processes. However, our ability systematically translate these findings into biological pathways remains limited. Here, we combine rapid loss-of-function mutagenesis Alzheimer’s risk and behavioural pharmacology in zebrafish predict disrupted processes candidate therapeutics. FramebyFrame , expanded package for the analysis larval behaviours, revealed decreased night-time sleep was common F0 knockouts all four late-onset tested. We developed an online tool, ZOLTAR which compares any fingerprint a library fingerprints from larvae treated 3677 compounds. successfully predicted sorl1 mutants have serotonin signalling identified betamethasone as drug normalises excessive day-time presenilin-2 knockout minimal side effects. Predictive offers general framework rapidly link disease-associated pathways.

Язык: Английский

Процитировано

0
What are the reasons for the repeated failures of clinical trials with anti-amyloid drugs for AD treatment? DOI Creative Commons
Orestes Vicente Forlenza, Breno José Alencar Pires Barbosa

Dementia & Neuropsychologia, Год журнала: 2025, Номер 19

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Lecanemab: turning point, or status quo? An ethics perspective DOI Open Access
Timothy Daly

Brain, Год журнала: 2023, Номер 146(9), С. e71 - e72

Опубликована: Март 21, 2023

Journal Article Lecanemab: turning point, or status quo? An ethics perspective Get access Timothy Daly Science Norms Democracy UMR 8011, Sorbonne Universite, 75005 Paris, FranceBioethics Program, FLACSO Argentina, Buenos Aires, C1050 AAN, Argentina Correspondence to: Daly, PhD Université 1 Rue Victor Cousin 75005, France E-mail: [email protected] https://orcid.org/0000-0003-1650-242X Search for other works by this author on: Oxford Academic PubMed Google Scholar Brain, Volume 146, Issue 9, September 2023, Pages e71–e72, https://doi.org/10.1093/brain/awad094 Published: 21 March 2023 history Received: 19 February Accepted: 16 Corrected and typeset: 18 April

Язык: Английский

Процитировано

10
Non-canonical pathways associated to Amyloid beta and tau protein dyshomeostasis in Alzheimer’s disease: A narrative review DOI Creative Commons

Anna Maggiore,

Valentina Latina, Maria D’Erme

и другие.

Ageing Research Reviews, Год журнала: 2024, Номер 102, С. 102578 - 102578

Опубликована: Ноя. 13, 2024

Alzheimer's Disease (AD) is the most common form of dementia among elderly people. This disease imposes a significant burden on healthcare system, society, and economy due to increasing global aging population. Current trials with drugs or bioactive compounds aimed at reducing cerebral Amyloid beta (Aβ) plaques tau protein neurofibrillary tangles, which are two main hallmarks this devastating neurodegenerative disease, have not provided results in terms their neuropathological outcomes nor met expected clinical end-points. Ageing, genetic environmental risk factors, along different symptoms suggest that AD complex heterogeneous disorder multiple interconnected pathological pathways rather than single entity. In present review, we highlight discuss various non-canonical, Aβ-independent mechanisms, like gliosis, unhealthy dietary intake, lipid sugar signaling, cerebrovascular damage contribute onset development AD. We emphasize challenging traditional "amyloid cascade hypothesis" may improve our understanding age-related syndrome help fight progressive cognitive decline

Язык: Английский

Процитировано

3
It’s good to know what to BACE the specificity of your inhibitors on DOI Creative Commons
Aoife Murray,

Ana Muñiz-García,

Ivan Alić

и другие.

Journal of Clinical Investigation, Год журнала: 2024, Номер 134(16)

Опубликована: Авг. 14, 2024

Production, aggregation, and clearance of the amyloid β peptide (Aβ) are important processes governing initial pathogenesis Alzheimer's disease (AD). Inhibition β-site precursor protein (APP) cleaving enzyme (BACE1) (one two key proteases responsible for Aβ production) as an AD-therapeutic approach so far has failed to yield a successful drug. BACE1 its homologue BACE2 frequently inhibited by same inhibitors. Several genetic cerebral organoid modeling studies suggest that dose-dependent AD-suppressing activity, which makes unwanted inhibition potentially counterproductive AD treatment. The in vivo effects cross have been impossible monitor because lack easily accessible pharmacodynamic marker specific cleavage. In this issue JCI, work led Stefan F. Lichtenthaler identifies soluble VEGFR3 (sVEGFR3) plasma activity not shared with BACE1.

Язык: Английский

Процитировано

2
Cell invasive amyloid assemblies from SARS-CoV-2 peptides can form multiple polymorphs with varying neurotoxicity DOI
Oana Sanislav,

Rina Tetaj,

Metali

и другие.

Nanoscale, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Preformed amyloid seeds increase the stability and toxicity of peptide amyloids formed from viral proteins SARS-CoV-2, these protein may cause some neurological symptoms COVID-19.

Язык: Английский

Процитировано

2
From experimental studies to computational approaches: recent trends in designing novel therapeutics for amyloidogenesis DOI
Pooja Ghosh, Aritra Kundu, Debabani Ganguly

и другие.

Journal of Materials Chemistry B, Год журнала: 2024, Номер unknown

Опубликована: Дек. 12, 2024

This review highlights the integration of various experimental and computational methods to control amyloid aggregation process. We believe that this article will help researchers develop novel therapeutic influence protein aggregation.

Язык: Английский

Процитировано

2