Aβ ‐induced excessive mitochondrial fission drives type H blood vessels injury to aggravate bone loss in APP/PS1 mice with Alzheimer's diseases DOI Creative Commons
Weidong Zhang, Fan Ding,

Xing Rong

et al.

Aging Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 16, 2024

Abstract Alzheimer's diseases (AD) patients suffer from more serious bone loss than cognitively normal subjects at the same age. Type H blood vessels were tightly associated with homeostasis. However, few studies have concentrated on vascular alteration and its role in AD‐related loss. In this study, APP/PS1 mice (4‐ 8‐month‐old) age‐matched wild‐type used to assess Transmission electron microscopy, immunofluorescence staining iGPS 1.0 software database utilized investigate molecular mechanism. Mitochondrial division inhibitor (Mdivi‐1) GSK‐3β (LiCl) rescue type injury verify Our results revealed that exhibited during ageing. The vessel injury, especially vessels, was accompanied by impaired vascularized osteogenesis mice. Further exploration indicated beta‐amyloid (Aβ) promoted apoptosis of endothelial cells (ECs) resulted injury. Mechanistically, Aβ‐induced excessive mitochondrial fission found be essential for ECs. identified as a key regulatory target findings delineated drives leading aggravate emerges potential therapeutic strategy.

Language: Английский

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier DOI Creative Commons
Shuai Zha, Haitao Liu, Hengde Li

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(3), P. 1820 - 1845

Published: Jan. 9, 2024

The blood–brain barrier (BBB) is a specialized semipermeable structure that highly regulates exchanges between the central nervous system parenchyma and blood vessels. Thus, BBB also prevents passage of various forms therapeutic agents, nanocarriers, their cargos. Recently, many multidisciplinary studies focus on developing cargo-loaded nanoparticles (NPs) to overcome these challenges, which are emerging as safe effective vehicles in neurotheranostics. In this Review, first we introduce anatomical physiological functions BBB. Second, present endogenous exogenous transport mechanisms by NPs cross We report nanomaterials, carriers, cargos, with detailed uptake permeability characteristics. Third, describe effect regulating size, shape, charge, surface ligands affect permeability, can be exploited enhance promote classify typical functionalized nanomaterials developed for crossing. Fourth, provide comprehensive review recent progress functional polymeric applications multimodal bioimaging, therapeutics, drug delivery. Finally, conclude discussing existing directions, future perspectives employing

Language: Английский

Citations

80
Amyloid-β and heart failure in Alzheimer’s disease: the new vistas DOI Creative Commons
Hayder M. Al‐kuraishy, Ghassan M. Sulaiman, Hamdoon A. Mohammed

et al.

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 4, 2025

Alzheimer’s disease (AD) is the most common cause of dementia and represents 75% all types. AD neuropathology due to progressive deposition extracellular amyloid-beta (A β ) peptide intracellular hyperphosphorylated tau protein. The accumulated Aβ forms amyloid plaques, while protein neurofibrillary tangles (NFTs). Both plaques NFTs are hallmarks neuropathology. fundamental mechanism involved in pathogenesis still elusive, although more conceivable theory. Aβ-induced neurodegeneration associated neuroinflammation, oxidative stress, endoplasmic reticulum stress (ER), mitochondrial dysfunction contribute development cognitive impairment dementia. Of note, not only originated from brain but also produced peripherally and, via blood–brain barrier (BBB), can accumulate result AD. It has been shown that cardiometabolic conditions such as obesity, type 2 diabetes (T2D), heart failure (HF) regarded possible risk factors for other types dementia, vascular HF-induced chronic cerebral hypoperfusion, inflammation induce progression Interestingly, a systemic causes which turn affects peripheral organs, including heart. through deranged BBB be transported into circulation heart, leading HF. These findings suggest close relationship between However, exact AD-induced HF fully elucidated. Therefore, this review aims discuss link regarding potential role

Language: Английский

Citations

4
Evaluation and targeting of amyloid precursor protein (APP)/amyloid beta (Aβ) axis in amyloidogenic and non-amyloidogenic pathways: A time outside the tunnel DOI
Hayder M. Al‐kuraishy, Majid S. Jabir, Ali I. Al‐Gareeb

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 92, P. 102119 - 102119

Published: Nov. 4, 2023

Language: Английский

Citations

26
Unraveling the transcriptomic landscape of brain vascular cells in dementia: A systematic review DOI Creative Commons
Michael D.E. Sewell,

Nela Fialova,

Axel Montagne

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract INTRODUCTION Cerebrovascular dysfunction plays a critical role in the pathogenesis of dementia and related neurodegenerative disorders. Recent omics‐driven research has revealed associations between vascular abnormalities transcriptomic alterations brain cells, particularly endothelial cells (ECs) pericytes (PCs). However, impact these molecular changes on remains unclear. METHODS We conducted comparative analysis gene expression ECs PCs across conditions, including Alzheimer's disease (AD), Huntington's disease, arteriovenous malformation, utilizing data from published postmortem human tissue studies. RESULTS identified differentially expressed genes (DEGs) consistently dysregulated pathologies. Notably, several DEGs are linked to cell zonation genetic risks for AD cerebral small vessel disease. DISCUSSION Our findings provide insights into cellular mechanisms underlying dementia, highlight knowledge gaps, suggest potential novel therapeutic targets, not previously investigated this context. Highlights Systematic review single‐nuclear RNA‐sequencing (snRNA‐seq) Identify overlapping multiple types Examine functional relevance with risk common DEGs. Outline future directions omics field.

Language: Английский

Citations

0
Design, synthesis, and activity evaluation of novel multitargeted l‐tryptophan derivatives with powerful antioxidant activity against Alzheimer's disease DOI
Xianghao Zeng, Shaobing Cheng, Huilan Li

et al.

Archiv der Pharmazie, Journal Year: 2024, Volume and Issue: 357(5)

Published: Jan. 30, 2024

Alzheimer's disease (AD) is a multifactorial neurological disease, and the multitarget directed ligand (MTDL) strategy may be an effective approach to delay its progression. Based on this strategy, 27 derivatives of l-tryptophan, 3a-1-3d-1, were designed, synthesized, evaluated for their biological activity. Among them, IC

Language: Английский

Citations

1
Aβ ‐induced excessive mitochondrial fission drives type H blood vessels injury to aggravate bone loss in APP/PS1 mice with Alzheimer's diseases DOI Creative Commons
Weidong Zhang, Fan Ding,

Xing Rong

et al.

Aging Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 16, 2024

Abstract Alzheimer's diseases (AD) patients suffer from more serious bone loss than cognitively normal subjects at the same age. Type H blood vessels were tightly associated with homeostasis. However, few studies have concentrated on vascular alteration and its role in AD‐related loss. In this study, APP/PS1 mice (4‐ 8‐month‐old) age‐matched wild‐type used to assess Transmission electron microscopy, immunofluorescence staining iGPS 1.0 software database utilized investigate molecular mechanism. Mitochondrial division inhibitor (Mdivi‐1) GSK‐3β (LiCl) rescue type injury verify Our results revealed that exhibited during ageing. The vessel injury, especially vessels, was accompanied by impaired vascularized osteogenesis mice. Further exploration indicated beta‐amyloid (Aβ) promoted apoptosis of endothelial cells (ECs) resulted injury. Mechanistically, Aβ‐induced excessive mitochondrial fission found be essential for ECs. identified as a key regulatory target findings delineated drives leading aggravate emerges potential therapeutic strategy.

Language: Английский

Citations

0