APP antisense oligonucleotides are effective in rescuing mitochondrial phenotypes in human iPSC‐derived trisomy 21 astrocytes

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(1)

Опубликована: Янв. 1, 2025

Antisense oligonucleotides (ASOs) have shown promise in reducing amyloid precursor protein (APP) levels neurons, but their effects astrocytes, key contributors to neurodegenerative diseases, remain unclear. This study evaluates the efficacy of APP ASOs astrocytes derived from an individual with Down syndrome (DS), a population at high risk for Alzheimer's disease (AD). Human induced pluripotent stem cells (hiPSCs) healthy and DS were differentiated into astrocytes. Astrocytes treated 10 days, quantified. Mitochondrial morphology superoxide production analyzed using super-resolution confocal microscopy. significantly reduced both control individuals. In treatment restored mitochondrial health, increasing number size while production. effectively reduce improve health suggesting potential as therapeutic approach DS-related AD. Further vivo studies are required confirm these findings. human iPSC-derived ASO rescues phenotypes trisomy 21 supports therapy syndrome-related disease.

Язык: Английский

Neuron-Astrocyte Interactions in Aging and Alzheimer's Disease: Dysregulation of Amyloid Precursor Protein

Ageing & Longevity, Год журнала: 2025, Номер 2. 2025, С. 117 - 128

Опубликована: Фев. 27, 2025

Amyloid precursor protein (APP) is central to Alzheimer's disease (AD) by its role in Aβ build-up and neuronal astrocytic malfunction. The major risk factor for late-onset AD aging, which increases APP processing both neurons astrocytes, consequently production. This focused review covers the subjects of how aging affect dynamics within cell types astrocytes dysfunction can enhance neuroinflammation injury. We discuss interplay between brains, where bi-directional cellular interactions accelerate neurodegeneration. Keywords: protein, Alzheimer`s disease, amyloid beta, neurons, neuroinflammation, reactive astrogliosis

Язык: Английский

Interrogating mediators of single-cell transcriptional changes in the acute damaged cerebral cortex: Insights into endothelial-astrocyte interactions

Molecular and Cellular Neuroscience, Год журнала: 2025, Номер unknown, С. 104003 - 104003

Опубликована: Март 1, 2025

Язык: Английский