The amyloid peptide β disrupts intercellular junctions and increases endothelial permeability in a NADPH oxidase 1-dependent manner

Tarafdar, Anuradha; Wolska, Nina; Schlüter, Hartmut; Pula, Giordano

doi:10.1016/j.redox.2022.102287

Cited by 5 publications

(6 citation statements)

References 66 publications

(80 reference statements)

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“…Interestingly, it seems that sAPPα-APP interactions induce the PI3K/Akt pathway via Gαo activation, and that APP works like GPCR and sAPPα works like its agonist ( Figure 4 ) [ 47 ]. GNG10 is differentially expressed in the hippocampus of AD [ 48 , 49 ].…”

Section: Resultsmentioning

confidence: 99%

1-L Transcription in Alzheimer’s Disease

Nahálka

2022

CIMB

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Alzheimer’s disease is a very complex disease and better explanations and models are needed to understand how neurons are affected and microglia are activated. A new model of Alzheimer’s disease is presented here, the β-amyloid peptide is considered an important RNA recognition/binding peptide. 1-L transcription revealed compatible sequences with AAUAAA (PAS signal) and UUUC (class III ARE rich in U) in the Aβ peptide, supporting the peptide–RNA regulatory model. When a hypothetical model of fibril selection with the prionic character of amyloid assemblies is added to the peptide-RNA regulatory model, the downregulation of the PI3K-Akt pathway and the upregulation of the PLC-IP3 pathway are well explained. The model explains why neurons are less protected from inflammation and why microglia are activated; why mitochondria are destabilized; why the autophagic flux is destabilized; and why the post-transcriptional attenuation of the axonal signal “noise” is interrupted. For example, the model suggests that Aβ peptide may post-transcriptionally control ELAVL2 (ELAV-like RNA binding protein 2) and DCP2 (decapping mRNA protein 2), which are known to regulate RNA processing, transport, and stability.

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Section: Resultsmentioning

confidence: 99%

1-L Transcription in Alzheimer’s Disease

Nahálka

2022

CIMB

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“…Of note is the fact that the concentrations of Aβ 1–42 used in this study are higher than the physiological concentration of Aβ 40/42 in the blood [ 38 ]. However, we did not observe any defined mechanism of Aβ 1–42 localization.…”

Section: Discussionmentioning

confidence: 99%

Effects of Amyloid Beta (Aβ) Oligomers on Blood–Brain Barrier Using a 3D Microfluidic Vasculature-on-a-Chip Model

Uzoechi,

Collins,

Badeaux

et al. 2024

Applied Sciences

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The disruption of the blood–brain barrier (BBB) in Alzheimer’s Disease (AD) is largely influenced by amyloid beta (Aβ). In this study, we developed a high-throughput microfluidic BBB model devoid of a physical membrane, featuring endothelial cells interacting with an extracellular matrix (ECM). This paper focuses on the impact of varying concentrations of Aβ1–42 oligomers on BBB dysfunction by treating them in the luminal. Our findings reveal a pronounced accumulation of Aβ1–42 oligomers at the BBB, resulting in the disruption of tight junctions and subsequent leakage evidenced by a barrier integrity assay. Additionally, cytotoxicity assessments indicate a concentration-dependent increase in cell death in response to Aβ1–42 oligomers (LC50 ~ 1 µM). This study underscores the utility of our membrane-free vascular chip in elucidating the dysfunction induced by Aβ with respect to the BBB.

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“…NADPH oxidase 1 has been demonstrated to play a pivotal role in mediating amyloid β-induced damage to the endothelial barrier [88]. Similarly, the involvement of NOX2 in the generation of reactive oxygen species, ultimately leading to the disruption of BBB integrity, has been substantiated.…”

Section: Oxidative Stressmentioning

confidence: 96%

Optogenetics in Alzheimer’s Disease: Focus on Astrocytes

Mitroshina,

Kalinina,

Vedunova

2023

Antioxidants

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Alzheimer’s disease (AD) is the most common form of dementia, resulting in disability and mortality. The global incidence of AD is consistently surging. Although numerous therapeutic agents with promising potential have been developed, none have successfully treated AD to date. Consequently, the pursuit of novel methodologies to address neurodegenerative processes in AD remains a paramount endeavor. A particularly promising avenue in this search is optogenetics, enabling the manipulation of neuronal activity. In recent years, research attention has pivoted from neurons to glial cells. This review aims to consider the potential of the optogenetic correction of astrocyte metabolism as a promising strategy for correcting AD-related disorders. The initial segment of the review centers on the role of astrocytes in the genesis of neurodegeneration. Astrocytes have been implicated in several pathological processes associated with AD, encompassing the clearance of β-amyloid, neuroinflammation, excitotoxicity, oxidative stress, and lipid metabolism (along with a critical role in apolipoprotein E function). The effect of astrocyte–neuronal interactions will also be scrutinized. Furthermore, the review delves into a number of studies indicating that changes in cellular calcium (Ca2+) signaling are one of the causes of neurodegeneration. The review’s latter section presents insights into the application of various optogenetic tools to manipulate astrocytic function as a means to counteract neurodegenerative changes.

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The amyloid peptide β disrupts intercellular junctions and increases endothelial permeability in a NADPH oxidase 1-dependent manner

Cited by 5 publications

References 66 publications

1-L Transcription in Alzheimer’s Disease

1-L Transcription in Alzheimer’s Disease

Effects of Amyloid Beta (Aβ) Oligomers on Blood–Brain Barrier Using a 3D Microfluidic Vasculature-on-a-Chip Model

Optogenetics in Alzheimer’s Disease: Focus on Astrocytes

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