Hydroxyl chalcone derivative DK02 as a multi‐target‐directed ligand for Alzheimer's disease: A preclinical study in zebrafish DOI

Balasubramanian Haridevamuthu,

Ankit Kumar Bharti, S.P. Ramya Ranjan Nayak

и другие.

British Journal of Pharmacology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 22, 2024

Background and Purpose Alzheimer's disease (AD) is a widespread neurodegenerative condition characterized by amyloid‐beta (Aβ) plaques tau protein aggregates, leading to significant cognitive decline. Existing treatments primarily offer symptomatic relief, underscoring the urgent need for novel therapies that address multiple AD pathways. This study evaluates efficacy of DK02, hydroxyl chalcone derivative, in scopolamine‐induced dementia model zebrafish, hypothesizing it targets several mechanisms simultaneously. Experimental Approach We employed blend experiments, including silico docking, vitro enzyme inhibition assays vivo zebrafish models, assess therapeutic effects DK02. Methods included molecular docking forecast interaction sites, acetylcholinesterase (AChE) testing, various behavioural histopathological analyses gauge DK02's neuroprotective impacts. Key Results DK02 emerged as potent AChE inhibitor via virtual screening, significantly enhanced functions improving memory retention reducing anxiety‐like behaviours. also displayed strong antioxidant properties, oxidative stress‐induced neuronal damage. Histopathological analysis confirmed its showing decreased amyloid plaque burden mitigated structural brain Conclusion Implications shows promise multi‐target‐directed ligand AD, offering new path simultaneously addressing cholinergic, Its potential enhance curtail neurodegeneration suggests advantages over current treatments. Further research into long‐term impacts essential development therapy.

Язык: Английский

Integrating amyloid and tau imaging with proteomics and genomics in Alzheimer’s disease DOI Creative Commons

Gabriele Vilkaite,

Jacob W. Vogel, Niklas Mattsson

и другие.

Cell Reports Medicine, Год журнала: 2024, Номер 5(9), С. 101735 - 101735

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

7
The role of PI3K signaling pathway in Alzheimer’s disease DOI Creative Commons
Jingying Pan,

Yao Qi,

Yankai Wang

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 16

Опубликована: Сен. 27, 2024

Alzheimer’s disease (AD) is a debilitating progressively neurodegenerative disease. The best-characterized hallmark of AD, which marked by behavioral alterations and cognitive deficits, the aggregation deposition amyloid-beta (Aβ) hyper-phosphorylated microtubule-associated protein Tau. Despite decades experimental progress, control rate AD remains poor, more precise deciphering needed for potential therapeutic targets signaling pathways involved. In recent years, phosphoinositide 3-kinase (PI3K) Akt have been recognized their role in neuroprotective effect various agents, glycogen synthase kinase 3 (GSK3), downstream enzyme, also crucial tau phosphorylation Aβ deposition. An overview function PI3K/Akt pathway pathophysiology provided this review, along with discussion developments pharmaceuticals herbal remedies that target pathway. conclusion, despite challenges hurdles, cumulative findings novel agents axis are expected to hold promise advancing prevention treatment.

Язык: Английский

Процитировано

6
Cell–type specific profiling of human entorhinal cortex at the onset of Alzheimer's disease neuropathology DOI Creative Commons
Patricia Rodriguez‐Rodriguez, Wei Wang,

Christina Tsagkogianni

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Neurons located in layer II of the entorhinal cortex (ECII) are primary site pathological tau accumulation and neurodegeneration at preclinical stages Alzheimer's disease (AD). Exploring alterations that underlie early degeneration these cells is essential to develop therapies curb before symptom onset. Here we performed cell-type specific profiling human EC onset AD neuropathology. We identify an response amyloid pathology by microglia oligodendrocytes. Importantly, provide first insight into neuronal coincide with incipient pathology: signaling pathway for Reelin, recently shown be a major resilience gene dysregulated ECII neurons, while secreted synaptic organizer molecules NPTX2 CBLN4, emerging biomarkers, downregulated surrounding neurons. By uncovering complex multicellular landscape stages, this study paves way detailed characterization mechanisms governing NFT formation opens long-needed novel therapeutic avenues.

Язык: Английский

Процитировано

0
IGF1R/ARRB1 Mediated Regulation of ERK and cAMP Pathways in Response to Aβ Unfolds Novel Therapeutic Avenue in Alzheimer’s Disease DOI Creative Commons
Priyanka Sengupta, Debashis Mukhopadhyay

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Язык: Английский

Процитировано

0
Multi-cohort cerebrospinal fluid proteomics identifies robust molecular signatures across the Alzheimer disease continuum DOI Creative Commons
Muhammad Ali, Jigyasha Timsina, Daniel Western

и другие.

Neuron, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Changes in β-amyloid (Aβ) and hyperphosphorylated tau (T) brain cerebrospinal fluid (CSF) precede Alzheimer's disease (AD) symptoms, making the CSF proteome a potential avenue to understand pathophysiology facilitate reliable diagnostics therapies. Using AT framework three-stage study design (discovery, replication, meta-analysis), we identified 2,173 analytes (2,029 unique proteins) dysregulated AD. Of these, 865 (43%) were previously reported, 1,164 (57%) are novel. The proteins cluster four different pseudo-trajectories groups spanning AD continuum enriched pathways including neuronal death, apoptosis, phosphorylation (early stages), microglia dysregulation endolysosomal dysfunction (mid plasticity longevity microglia-neuron crosstalk (late stages). machine learning, created validated highly accurate replicable (area under curve [AUC] > 0.90) models that predict biomarker positivity clinical status. These can also identify people will convert

Язык: Английский

Процитировано

0
Decoding microglial functions in Alzheimer’s disease: insights from human models DOI
Chandrika Rao, Stefan Semrau, Valentina Fossati

и другие.

Trends in Immunology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Ginkgo biloba Extract GBE50 ameliorates cerebrovascular dysfunction and cognitive impairment in a mouse model of Alzheimer's disease DOI
Ting Yu,

Zijie Wei,

Jing Wang

и другие.

Phytomedicine, Год журнала: 2025, Номер unknown, С. 156646 - 156646

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Cerebrospinal fluid proteomics identification of biomarkers for amyloid and tau PET stages DOI Creative Commons
Zhibo Wang, Yuhan Chen,

Kezhuang Gong

и другие.

Cell Reports Medicine, Год журнала: 2025, Номер unknown, С. 102031 - 102031

Опубликована: Март 1, 2025

Accurate staging of Alzheimer's disease (AD) pathology is crucial for therapeutic trials and prognosis, but existing fluid biomarkers lack specificity, especially assessing tau deposition severity, in amyloid-beta (Aβ)-positive patients. We analyze cerebrospinal (CSF) samples from 136 participants the Disease Neuroimaging Initiative using more than 6,000 proteins. apply machine learning to predict AD pathological stages defined by amyloid positron emission tomography (PET). identify two distinct protein panels: 16 proteins, including neurofilament heavy chain (NEFH) SPARC-related modular calcium-binding 1 (SMOC1), that distinguished Aβ-negative/tau-negative (A-T-) A+ individuals nine such as HCLS1-associated X-1 (HAX1) glucose-6-phosphate isomerase (GPI), differentiated A+T+ A+T- stages. These signatures outperform established CSF (area under curve [AUC]: 0.92 versus 0.67-0.70) accurately predicted progression over a decade. The findings are validated both internal external cohorts. results underscore potential proteomic-based refine diagnostic criteria improve patient stratification clinical trials.

Язык: Английский

Процитировано

0
Cognitive Frailty: A Comprehensive Clinical Paradigm Beyond Cognitive Decline DOI
Mariagiovanna Cozza, Virginia Boccardi

Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102738 - 102738

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Extracellular particles: emerging insights into central nervous system diseases DOI Creative Commons
Shenyuan Chen, Qiaoliang Bao,

Wenrong Xu

и другие.

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 1, 2025

Extracellular particles (EPs), including extracellular vesicles (EVs) and non-vesicular (NVEPs), are multimolecular biomaterials released by cells that play a crucial role in intercellular communication. Recently, new subtypes of EPs associated with central nervous system (CNS), such as exophers supermeres have been identified. These provide perspectives for understanding the pathological progression CNS disorders confer potential diagnostic value liquid biopsies neurodegenerative diseases (NDs). Moreover, emerged promising drug delivery vehicles targeted platforms CNS-specific therapies. In this review, we delineate landscape EP their roles pathophysiology diseases. We also review recent advances EP-based diagnosis NDs highlight importance analytical single-particle resolution exploitation biomarkers. Furthermore, summarize application engineered EVs treatment outline underexplored NVEPs novel therapeutic agents.

Язык: Английский

Процитировано

0