The emergence of neurodegenerative diseases is connected to several pathogenic factors, including metal ions, amyloidogenic proteins, and reactive oxygen species. Recent studies suggest that cytotoxicity is caused by the small, dynamic, and metastable nature of early stage oligomeric species. This work introduces a small molecule-based red-emitting probe with smart features such as increased reactivities against multiple targets, metal-free amyloid-β (Aβ), and metal-bound amyloid-β (Aβ), and most importantly, early stage oligomeric species which are associated with the most common and widespread type of dementia, Alzheimer's disease (AD). Theoretical analyses like molecular dynamics simulation and molecular docking were performed to confirm the reactivity of the molecule toward Aβ and found some excellent interactions between the molecule and the peptide. The and cellular studies demonstrated that this highly biocompatible molecule effectively reduces the structural damage to mitochondria while shielding cells from apoptosis, scavenges ROS (reactive oxygen species), and attenuates multifaceted amyloid toxicity.

Download full-text PDF

Source
http://dx.doi.org/10.1021/acschemneuro.3c00473DOI Listing

Publication Analysis

Top Keywords

alzheimer's disease
8
reactive oxygen
8
oxygen species
8
early stage
8
stage oligomeric
8
oligomeric species
8
amyloid-β aβ
8
amyloid targeting
4
targeting red
4
red emitting
4

Similar Publications

The aetiology of Alzheimer's disease (AD) and Parkinson's disease (PD) are unknown and tend to manifest at a late stage in life; even though these neurodegenerative diseases are caused by different affected proteins, they are both characterized by neuroinflammation. Links between bacterial and viral infection and AD/PD has been suggested in several studies, however, few have attempted to establish a link between fungal infection and AD/PD. In this study we adopted a nanopore-based sequencing approach to characterise the presence or absence of fungal genera in both human brain tissue and cerebrospinal fluid (CSF).

View Article and Find Full Text PDF

Neurodegeneration in Huntington's disease (HD) is accompanied by the aggregation of fragments of the mutant huntingtin protein, a biomarker of disease progression. A particular pathogenic role has been attributed to the aggregation-prone huntingtin exon 1 (HTTex1), generated by aberrant splicing or proteolysis, and containing the expanded polyglutamine (polyQ) segment. Unlike amyloid fibrils from Parkinson's and Alzheimer's diseases, the atomic-level structure of HTTex1 fibrils has remained unknown, limiting diagnostic and treatment efforts.

View Article and Find Full Text PDF

Impaired muscle mitochondrial oxidative capacity is associated with future cognitive impairment, and higher levels of PET and blood biomarkers of Alzheimer's disease and neurodegeneration. Here, we examine its associations with up to over a decade-long changes in brain atrophy and microstructure. Higher in vivo skeletal muscle oxidative capacity via MR spectroscopy (post-exercise recovery rate, k) is associated with less ventricular enlargement and brain aging progression, and less atrophy in specific regions, notably primary sensorimotor cortex, temporal white and gray matter, thalamus, occipital areas, cingulate cortex, and cerebellum white matter.

View Article and Find Full Text PDF

Background And Purpose: In idiopathic normal pressure hydrocephalus (iNPH) patients, cerebrospinal fluid (CSF) flow is typically evaluated with a cardiac-gated two-dimensional (2D) phase-contrast (PC) MRI through the cerebral aqueduct. This approach is limited by the evaluation of a single location and does not account for respiration effects on flow. In this study, we quantified the cardiac and respiratory contributions to CSF movement at multiple intracranial locations using a real-time 2D PC-MRI and evaluated the diagnostic value of CSF dynamics biomarkers in classifying iNPH patients.

View Article and Find Full Text PDF

Background: Atrial fibrillation (AF) is associated with cognitive decline. Use of oral anticoagulant (OAC) medications offers a lower risk of dementia, but it is unclear whether differences exist between types of OAC agents.

Objective: This was a secondary analysis to explore whether the progression from normal cognition to mild cognitive impairment to dementia differs between adults with AF on warfarin versus non-vitamin K inhibitors medications (NOACs) using data extracted from the National Alzheimer's Coordinating Center clinical case series.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!