Blood-based multivariate methylation risk score for cognitive impairment and dementia DOI Open Access
J.C. Koetsier, Rachel Cavill, Rick A. Reijnders

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 28, 2023

ABSTRACT INTRODUCTION Given the established association between DNA methylation and pathophysiology of dementia its plausible role as a molecular mediator lifestyle environment, blood-derived data could enable early detection risk. METHODS In conjunction with an extensive array machine learning techniques, we employed whole blood genome-wide surrogate for 14 modifiable non-modifiable factors in assessment risk two independent cohorts Alzheimer’s disease (AD) Parkinson’s (PD). RESULTS We multivariate score (MMRS) to identify status mild cognitive impairment (MCI) cross-sectionally, age sex. further demonstrated significant predictive capability this prospective onset decline AD PD. DISCUSSION Our work shows potential employing

Language: Английский

A study to determine the effect of nano-selenium and thymoquinone on the Nrf2 gene expression in Alzheimer’s disease DOI Creative Commons
Doha El‐Sayed Ellakwa,

Laila Ahmed Rashed,

Ola Ali

et al.

Future Science OA, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 31, 2025

Alzheimer's disease is a developing public health concern in aging communities that affects sizable section of the global population. The risk increases with age; it one-third males and two-thirds women. This research attempts to assess effect nano-selenium thymoquinone on Nrf2 gene expression levels (AD). There were five identical groups 50 albino male rats: control group was healthy; an AD positive group; received (5 mg/kg); (2 both. duration treatment 4 weeks. brain tissues evaluated using real-time PCR. mean nano-selenium-treated rats, thymoquinone-treated rats given both treatments all increased significantly compared no treatment. study showed elevated AD.

Language: Английский

Citations

3
Bioactive Decellularized Extracellular Matrix Platform Integrating Multifunctional Nanozymes and Cell-Laden Microgels for Acute Liver Failure Treatment DOI
Gang Xiao, Jiabin Zhang,

Tong Lin

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Mesenchymal stem cell (MSC) therapy has emerged as a promising alternative approach for treating acute liver failure (ALF) while confronting the shortage of low efficiency and poor engraftment within hostile milieu. In this study, we establish bioactive decellularized extracellular matrix (dECM) platform that incorporates dihydrolipoic acid (DHLA)-protected Pt nanoclusters doped with Cu (PtCu-DHLA) nanozymes cell-laden microgels. The PtCu-DHLA nanozymes, selected their versatility, function antioxidant, anti-inflammatory, pro-proliferative, pro-angiogenic agents, enhancing ALF alleviation providing an optimal microenvironment MSC transplantation. Additionally, methacrylic anhydride (MA)-modified porcine liver-derived (PLdECM) hydrogel (PLdECMMA) been developed construction microgels via microfluidic devices. Interferon γ (IFNγ) preconditioned MSCs encapsulated in PLdECMMA exhibit enhanced immunomodulating activity prolonged survival. are codelivered by leveraging PLdECM orthotopic transplanted dECM enables efficient successful rescue CCl4-induced counteracting oxidative stress, suppressing inflammatory storms, promoting cellular regeneration. Overall, study highlights synergistic reinforced strategy combines biomimetic therapy, offering significant potential treatment broader applications regenerative medicine.

Language: Английский

Citations

1
Therapeutic effect of nicotinamide mononucleotide on Alzheimer’s disease through activating autophagy and anti-oxidative stress DOI Open Access

Rui-Yin Ma,

Li Li, Hui Yang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117199 - 117199

Published: July 24, 2024

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of β-amyloid (Aβ) plaques and neurofibrillary tangles composed tau protein in brain. These neuropathological hallmarks contribute to cognitive impairment inducing neuronal loss cerebral cortex hippocampus. Unfortunately, current therapeutic approaches only target symptomatic relief do not impede progression. Nicotinamide mononucleotide (NMN), precursor nicotinamide adenine dinucleotide (NAD

Language: Английский

Citations

5
Blood‐based multivariate methylation risk score for cognitive impairment and dementia DOI Creative Commons
J.C. Koetsier, Rachel Cavill, Rick A. Reijnders

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

The established link between DNA methylation and pathophysiology of dementia, along with its potential role as a molecular mediator lifestyle environmental influences, positions blood-derived promising tool for early dementia risk detection.

Language: Английский

Citations

4
Deciphering novel mitochondrial signatures: multi-omics analysis uncovers cross-disease markers and oligodendrocyte pathways in Alzheimer’s disease and glioblastoma DOI Creative Commons
Xuan Xu, Jiaqi Wang, Tong Chen

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Feb. 13, 2025

Introduction Alzheimer’s disease (AD) and glioblastoma (GBM) are severe neurological disorders that pose significant global healthcare challenges. Despite extensive research, the molecular mechanisms, particularly those involving mitochondrial dysfunction, remain poorly understood. A major limitation in current studies is lack of cell-specific markers effectively represent dynamics AD GBM. Methods In this study, we analyzed single-cell transcriptomic data using 10 machine learning algorithms to identify mitochondria-associated markers. We validated these through integration gene expression methylation across diverse cell types. Our dataset comprised single-nucleus RNA sequencing (snRNA-seq) from patients, (scRNA-seq) GBM additional DNA ROSMAP, ADNI, TCGA, CGGA cohorts. Results analysis identified four cross-disease markers: EFHD1, SASH1, FAM110B, SLC25A18 . These showed both shared unique profiles GBM, suggesting a common mechanism contributing diseases. Additionally, oligodendrocytes their interactions with astrocytes were implicated progression, APP signaling pathway. Key hub genes, such as HS6ST3 TUBB2B , different cellular subpopulations, highlighting co-expression network linked function.

Language: Английский

Citations

0
Microglial NOX2 as a therapeutic target in traumatic brain injury: Mechanisms, Consequences, and Potential for Neuroprotection DOI

Nargis Bano,

Sameera Khan,

Shakir Ahamad

et al.

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102735 - 102735

Published: March 1, 2025

Language: Английский

Citations

0
Emerging small molecule inhibitors of Bach1 as therapeutic agents: Rationale, recent advances, and future perspectives DOI Creative Commons
Dmitry M. Hushpulian, Navneet Ammal Kaidery, Debashis Dutta

et al.

BioEssays, Journal Year: 2023, Volume and Issue: 46(1)

Published: Nov. 2, 2023

Abstract The transcription factor Nrf2 is the master regulator of cellular stress response, facilitating expression cytoprotective genes, including those responsible for drug detoxification, immunomodulation, and iron metabolism. FDA‐approved activators, Tecfidera Skyclarys patients with multiple sclerosis Friedreich's ataxia, respectively, are non‐specific alkylating agents exerting side effects. under feedback regulation through its target gene, transcriptional repressor Bach1. Specifically, in Parkinson's disease other neurodegenerative diseases Bach1 dysregulation, excessive accumulation interferes activation. a heme sensor protein, which, upon binding, targeted proteasomal degradation, relieving repression genes. Ideally, combination stabilization inhibition necessary to achieve full therapeutic benefits Here, we discuss recent advances future perspectives developing small molecule inhibitors Bach1, highlighting significance Bach1/Nrf2 signaling pathway as promising neurotherapeutic strategy.

Language: Английский

Citations

7
Crystal Violet Selectively Detects Aβ Oligomers but Not Fibrils In Vitro and in Alzheimer’s Disease Brain Tissue DOI Creative Commons
Kanchana Karunarathne, Teresa R. Kee, Hanna Jeon

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(6), P. 615 - 615

Published: May 23, 2024

Deposition of extracellular Amyloid Beta (Aβ) and intracellular tau fibrils in post-mortem brains remains the only way to conclusively confirm cases Alzheimer’s Disease (AD). Substantial evidence, though, implicates small globular oligomers instead as relevant biomarkers of, critical contributors to, clinical symptoms AD. Efforts verify utilize amyloid AD vivo have been limited by near-exclusive dependence on conformation-selective antibodies for oligomer detection. While yielded evidence role both Aβ AD, they are not suitable imaging vivo. Therefore, it would be desirable identify a set oligomer-selective molecules subsequent development into Positron Emission Tomography (PET) probes. Using kinetics-based screening assay, we that triarylmethane dye Crystal Violet (CV) is Aβ42 (AβOs) grown under near-physiological solution conditions vitro. In postmortem an mouse model human patients, demonstrate A11 antibody-positive but Thioflavin S (ThioS)-positive colocalize with CV staining, confirming vitro results. our kinetic screen represents robust approach identifying new classes candidates dyes (OSDs). Such OSDs, turn, provide promising starting points PET probes pre-mortem deposits humans.

Language: Английский

Citations

2
Disruption of Mitophagy Flux through the PARL-PINK1 Pathway by CHCHD10 Mutations or CHCHD10 Depletion DOI Creative Commons
Tian Liu,

Liam Wetzel,

Zexi Zhu

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(24), P. 2781 - 2781

Published: Dec. 7, 2023

Coiled-coil-helix-coiled-coil-helix domain-containing 10 (CHCHD10) is a nuclear-encoded mitochondrial protein which primarily mutated in the spectrum of familial and sporadic amyotrophic lateral sclerosis (ALS)–frontotemporal dementia (FTD). Endogenous CHCHD10 levels decline brains ALS–FTD patients, CHCHD10S59L mutation Drosophila induces dominant toxicity together with PTEN-induced kinase 1 (PINK1), critical for induction mitophagy. However, whether how variants regulate mitophagy flux mammalian brain unknown. Here, we demonstrate through vivo vitro models, as well human FTD tissue, that ALS/FTD-linked mutations (R15L S59L) impair Parkin recruitment, whereas wild-type (CHCHD10WT) normally enhances these measures. Specifically, show CHCHD10R15L reduce PINK1 by increasing PARL activity, CHCHD10WT produces opposite results its stronger interaction PARL, suppressing activity. Importantly, also TAR DNA-binding protein-43 (TDP-43) pathology disruption PARL–PINK1 pathway experimentally impairing promotes TDP-43 aggregation. Thus, provide herein new insights into regulation aggregation CHCHD10–PARL–PINK1 pathway.

Language: Английский

Citations

6
A comprehensive review on therapeutic potentials of photobiomodulation for neurodegenerative disorders DOI
Pooja Ramakrishnan, Aradhana Joshi,

Mohamed Fazil

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 336, P. 122334 - 122334

Published: Dec. 5, 2023

Language: Английский

Citations

3