The elimination of amyloid beta (Aβ) oligomers is a promising strategy for therapeutic drug development of Alzheimer's disease (AD). AD mouse models that develop Aβ pathology have been used to demonstrate in vivo efficacy of compounds that later failed in clinical development. Here, we analyze the concentration and size distribution of Aβ oligomers in different transgenic mouse models of AD and in human brain samples by surface-based fluorescence intensity distribution analysis (sFIDA), a highly sensitive method for detecting and quantitating protein aggregates. We demonstrate dose- and time-dependent oligomer elimination by the compound RD2 in mouse and human AD brain homogenates as sources of native Aβ oligomers. Such ex vivo target engagement analyses with mouse- and human-brain-derived oligomers have the potential to enhance the translational value from pre-clinical proof-of-concept studies to clinical trials.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9133466 | PMC |
| http://dx.doi.org/10.1016/j.xcrm.2022.100630 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Metabolically stable apelin analogs: development and functional role in water balance and cardiovascular function.
Clin Sci (Lond)
January 2025
Center for Interdisciplinary Research in Biology, College de France, Institut National de la Santé et de la Recherche Médicale, Paris, France.
Apelin, a (neuro) vasoactive peptide, plays a prominent role in controlling water balance and cardiovascular functions. Apelin and its receptor co-localize with vasopressin in magnocellular vasopressinergic neurons. Apelin receptors (Apelin-Rs) are also expressed in the collecting ducts of the kidney, where vasopressin type 2 receptors are also present.
View Article and Find Full Text PDFQuantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD).
J Vis Exp
January 2025
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Henry and Allison McCance Center for Brain Health, Department of Neurology, Massachusetts General Hospital, Harvard Medical School;
A method to quantitate the stabilization of Mitochondria-Associated endoplasmic reticulum Membranes (MAMs) in a 3-dimensional (3D) neural model of Alzheimer's disease (AD) is presented here. To begin, fresh human neuro progenitor ReN cells expressing β-amyloid precursor protein (APP) containing familial Alzheimer's disease (FAD) or naïve ReN cells are grown in thin (1:100) Matrigel-coated tissue culture plates. After the cells reach confluency, these are electroporated with expression plasmids encoding red fluorescence protein (RFP)-conjugated mitochondria-binding sequence of AKAP1(34-63) (Mito-RFP) that detects mitochondria or constitutive MAM stabilizers MAM 1X or MAM 9X that stabilize tight (6 nm ± 1 nm gap width) or loose (24 nm ± 3 nm gap width) MAMs, respectively.
View Article and Find Full Text PDF2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione protects against MPP-induced neurotoxicity by ameliorating oxidative stress, apoptosis and autophagy in SH-SY5Y cells.
Metab Brain Dis
January 2025
Key Laboratory of Longevity and Aging-Related Disease of Chinese Ministry of Education, Center for Translational Medicine, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China.
2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) is a cyclohexanedione compound extracted from the roots of Averrhoa carambola L. Several studies have documented its beneficial effects on diabetes, Alzheimer's disease, and cancer. However, its potential neuroprotective effects on Parkinson's disease (PD) have not yet been explored.
View Article and Find Full Text PDFAge-related differences in eye movements and the association with Archimedes spiral tracing performance in young and older adults.
Exp Brain Res
January 2025
Joseph J. Zilber College of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
Age-related hand motor impairments may critically depend on visual information though few studies have examined eye movements during tasks of hand function in older adults. The purpose of this study was to assess eye movements and their association with performance while tracing on a touchscreen in young and older adults. Eye movements of 21 young (age 20-38 years; 12 females, 9 males) and 20 older (65-85 years; 10 females, 10 males) adults were recorded while performing an Archimedes spiral tracing task, a common clinical assessment sensitive to age-associated impairments in hand function.
View Article and Find Full Text PDFAging with HIV and HIV-associated neurocognitive impairment.
AIDS
March 2025
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy.
Antiretroviral therapy (ART) is the most effective therapeutic intervention for HIV infection. With improved survival, comorbidities, including neuropsychiatric and HIV-associated neurocognitive impairment (NCI) are of increasing concern to aging people with HIV (PWH). The clinical features and the inter-individual variability of the aging process confound the elucidation of the diagnosis and underlying mechanisms of cognitive dysfunction in aging PWH.
View Article and Find Full Text PDFWant 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!