Amyloid-β: A potential mediator of aging-related vascular pathologies

Khan, Fazlullah; Qiu, Hongyu

doi:10.1016/j.vph.2023.107213

Cited by 4 publications

(3 citation statements)

References 131 publications

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“…54 The initial occurrence associated with AD is the accumulation of Aβ, which can lead to cerebral amyloid angiopathy. 55 The buildup of Aβ surrounding blood vessels has the potential to cause pericyte death 56 and altered astrocyte morphology, 57 consequently compromising BBB integrity (Figure 4B). 58 Another major pathology hallmark in AD is the presence of tau deposits.…”

Section: Bbb In Neurodegenerativementioning

confidence: 99%

“…AD is a prevalent neurological disorder, recognized as the primary cause of dementia . The initial occurrence associated with AD is the accumulation of Aβ, which can lead to cerebral amyloid angiopathy . The buildup of Aβ surrounding blood vessels has the potential to cause pericyte death and altered astrocyte morphology, consequently compromising BBB integrity (Figure B) .…”

Section: Abnormal Bbb Structure In Cns Diseasesmentioning

confidence: 99%

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Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

Zha,

Liu,

et al. 2024

ACS Nano

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

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Section: Bbb In Neurodegenerativementioning

confidence: 99%

Section: Abnormal Bbb Structure In Cns Diseasesmentioning

confidence: 99%

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

Zha,

Liu,

et al. 2024

ACS Nano

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“…complexes and is considered to be a major component of the senile plaques in the brains of patients with AD. [28] As depicted in…”

Section: T a B L Ementioning

confidence: 99%

Design, synthesis, and activity evaluation of novel multitargeted l‐tryptophan derivatives with powerful antioxidant activity against Alzheimer's disease

Zeng,

Cheng,

et al. 2024

Archiv der Pharmazie

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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, and evaluated for their biological activity. Among them, IC50 (inhibitor concentration resulting in 50% inhibitory activity) values of compounds 3a‐18 and 3b‐1 were 0.58 and 0.44 μM for human serum butyrylcholinesterase (hBuChE), respectively, and both of them exhibited more than 30‐fold selectivity for human serum acetylcholinesterase. Enzyme kinetics studies showed that these two compounds were mixed inhibitors of hBuChE. In addition, these two derivatives possessed extraordinary antioxidant activity in OH radical scavenging and oxygen radical absorption capacity fluorescein assays. Meanwhile, these compounds could also prevent β‐amyloid (Aβ) self‐aggregation and possessed low toxicity on PC12 and AML12 cells. Molecular modeling studies revealed that these two compounds could interact with the choline binding site, acetyl binding site, and peripheral anionic site to exert submicromolar BuChE inhibitory activity. In the vitro blood–brain barrier permeation assay, compounds 3a‐18 and 3b‐1 showed enough blood–brain barrier permeability. In drug‐likeness prediction, compounds 3a‐18 and 3b‐1 showed good gastrointestinal absorption and a low risk of human ether‐a‐go‐go‐related gene toxicity. Therefore, compounds 3a‐18 and 3b‐1 are potential multitarget anti‐AD lead compounds, which could work as powerful antioxidants with submicromolar selective inhibitory activity for hBuChE as well as prevent Aβ self‐aggregation.

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