Cannabidiol and Neurodegeneration: From Molecular Mechanisms to Clinical Benefits

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 100, P. 102386 - 102386

Published: July 4, 2024

Language: Английский

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Cerebrospinal fluid β2-microglobulin promotes the tau pathology through microglia–astrocyte communication in Alzheimer's disease

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 2, 2025

Cerebrospinal fluid (CSF) β2-microglobulin (β2M) has been demonstrated as an important factor in β-amyloid (Aβ) neurotoxicity and a potential target for Alzheimer's disease (AD). However, more investigation is required to ascertain the relationship between β2M glial activities AD pathogenesis. In this study, 211 participants from Neuroimaging Initiative (ADNI) with CSF Plasma β2M, fibrillary acidic protein (GFAP), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), Aβ42, phosphorylated-tau (P-tau) total tau (T-tau) were divided into four groups, stage 0, 1, 2, suspected non-AD pathology (SNAP) based National Institute Aging- Association (NIA-AA) criteria. Multiple linear regression, mixed effects models, causal mediation analyses bootstrapped 10,000 iterations used investigate underlying associations among biomarkers at baseline during longitudinal visit. concentration decreased amyloid 1 compared 0 increased neurodegeneration SNAP 1. Moreover, level was positively correlated Aβ42 (β = 0.230), P-tau 0.564), T-tau 0.603), GFAP 0.552), sTREM2 0.641) (all P < 0.001). only longitudinally change. The correlation of (proportion 25.4%, 0.001) 26.7%, partially mediated by participants, reproduced late-life individuals. Furthermore, astrocyte cascade also pathological (β2M → YKL-40 P-tau/T-tau, IE: 0.424—0.435, all Nevertheless, not significant. Additionally, there no association plasma biomarkers. dynamic associated neuroinflammation. might mediate pathology, complementing existing research effect providing new perspective treatment.

Language: Английский

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H4K12 lactylation-regulated NLRP3 is involved in cigarette smoke-accelerated Alzheimer-like pathology through mTOR-regulated autophagy and activation of microglia

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: 488, P. 137310 - 137310

Published: Jan. 21, 2025

Language: Английский

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Role of the transcription factor NRF2 in maintaining the integrity of the Blood-Brain Barrier

Fluids and Barriers of the CNS, Journal Year: 2024, Volume and Issue: 21(1)

Published: Nov. 21, 2024

The Blood-Brain Barrier (BBB) is a complex and dynamic interface that regulates the exchange of molecules cells between blood central nervous system. It undergoes structural functional throughout oxidative stress inflammation, which may compromise its integrity contribute to pathogenesis neurodegenerative diseases. Maintaining BBB utmost importance in preventing wide range neurological disorders. NRF2 main transcription factor cellular redox balance inflammation-related gene expression. has also demonstrated potential role regulating tight junction contributing inhibition ECM remodeling, by reducing expression several metalloprotease family members involved maintaining function. Overall, we review current insights on addressing protection against effects dysfunction, discuss involvement maintenance different neuropathological diseases, as well as, some activators have been used vitro vivo animal models for barrier dysfunction. Thus, emerging evidence suggests upregulation target genes could suppress stress, neuroinflammation, restore integrity, increase protection.

Language: Английский

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Design and synthesis three novel series of derivatives using natural acetylcholinesterase inhibitor-RLMS as template and in vitro, in vivo and in silico activities verification

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 286, P. 117309 - 117309

Published: Jan. 23, 2025

Language: Английский

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Cerebral microvascular density, blood-brain barrier permeability, and support for neuroinflammation indicate early aging in a Marfan syndrome mouse model

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 31, 2025

Introduction Marfan Syndrome (MFS) is a connective tissue disorder due to mutations in fibrillin-1 ( Fbn1 ), where missense mutation C1039G/+ ) can result systemic increases the bioavailability and signaling of transforming growth factor-β (TGF-β). In well-established mouse model MFS C1041G/+ pre-mature aging aortic wall progression root aneurysm are observed by 6-month-of-age. TGF-β has been implicated cerebrovascular dysfunction, loss blood-brain barrier (BBB) integrity, age-related neuroinflammation. We have reported that vascular mice could extend cerebrovasculature, peak blood flow velocity posterior cerebral artery (PCA) 6-month-old (6M) was reduced, similarly 12-month-old (12M) control mice. Case studies patients documented neurovascular manifestations, including intracranial aneurysms, stroke, arterial tortuosity, as well headaches migraines, with incidences pain chronic fatigue. Despite these significant clinical observations, investigation into dysfunction neuropathology remains limited. Methods Using 6M-control C57BL/6 6M-MFS healthy 12M-control male female mice, we test hypothesis abnormal protein expression associated altered microvascular density, BBB permeability, neuroinflammation PCA-perfused hippocampus, all indicative brain phenotype. Glut1 immunostaining used quantify IgG staining assess microglial counts evaluate Results staining, 12M-CTRL present decreased density dentate gyrus (DG), cornu ammonis 1 (CA1), 3 (CA3) regions hippocampus. exhibit increased permeability DG CA3 evident Immunoglobulin G (IgG) staining. No differences were detected between 6M show higher number microglia hippocampus compared age-matched pattern resembling Discussion This study represents first known indicates pathophysiology underlying leads crucial for identifying understanding MFS-associated neurological abnormalities, underscoring need research aimed at improving quality life managing symptoms related disorders.

Language: Английский

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Phytochemicals from Tomato (Solanum lycopersicum L.) By-Products

Published: Jan. 1, 2025

Language: Английский

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Advancing Blood–Brain Barrier-on-a-Chip Models Through Numerical Simulations

BioChip Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 3, 2024

Abstract Researchers have placed engineered or natural tissues within microfluidic chips originating the so-called organ-on-a-chip (OoC) devices. With this technology, organ models can be subjected to phenomena that replicate complex in vivo biological environment. Furthermore, OoC devices constitute a more valuable, cost-effective and ethical option when compared assays performed animal for disease research drug discovery. However, there are still many challenges replicating some organs/diseases vitro such as Blood–Brain Barrier (BBB), given its complexity structure. Despite difficulties, efforts been made develop improved BBB-on-a-chip investigate several neurological disorders. In present review, summary of progress development is provided focusing on importance using numerical simulations obtaining better planning experimental assays. addition, future perspectives current provided.

Language: Английский

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Exploring complexities of Alzheimer’s disease: New insights into molecular and cellular mechanisms of neurodegeneration and targeted therapeutic interventions

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 104, P. 102548 - 102548

Published: Oct. 16, 2024

Language: Английский

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Cerebral Microvascular Density, Permeability of the Blood-Brain Barrier, and Neuroinflammatory Responses Indicate Early Aging Characteristics in a Marfan Syndrome Mouse Model

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 2, 2024

Marfan Syndrome (MFS) is a connective tissue disorder due to mutations in fibrillin-1 (

Language: Английский

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