Protein Oxidation in Aging and Alzheimer’s Disease Brain DOI Creative Commons
Rukhsana Sultana, D. Allan Butterfield

Antioxidants, Journal Year: 2024, Volume and Issue: 13(5), P. 574 - 574

Published: May 7, 2024

Proteins are essential molecules that play crucial roles in maintaining cellular homeostasis and carrying out biological functions such as catalyzing biochemical reactions, structural proteins, immune response, etc. However, proteins also highly susceptible to damage by reactive oxygen species (ROS) nitrogen (RNS). In this review, we summarize the role of protein oxidation normal aging Alzheimer's disease (AD). The major emphasis review article is on carbonylation nitration AD mild cognitive impairment (MCI). oxidatively modified showed a strong correlation with reported changes brain structure, carbohydrate metabolism, synaptic transmission, energetics, etc., both MCI brains compared controls. Some were found be common targets observed during early stages AD, suggesting those might critical onset symptoms and/or formation pathological hallmarks AD. Further studies required fully elucidate progression pathogenesis

Language: Английский

Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration DOI
Rickie Patani, Giles E. Hardingham, Shane A. Liddelow

et al.

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(7), P. 395 - 409

Published: June 12, 2023

Language: Английский

Citations

233
Early Alzheimer’s disease pathology in human cortex involves transient cell states DOI Creative Commons
Vahid Gazestani, Tushar Kamath, Naeem Nadaf

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(20), P. 4438 - 4453.e23

Published: Sept. 1, 2023

Language: Английский

Citations

98
The role of astrocytic α7 nicotinic acetylcholine receptors in Alzheimer disease DOI
Igor C. Fontana, Amit Kumar, Agneta Nordberg

et al.

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(5), P. 278 - 288

Published: March 28, 2023

Language: Английский

Citations

47
Pathological phenotypes of astrocytes in Alzheimer’s disease DOI Creative Commons
Junhyung Kim, Ik Dong Yoo, Jaejoon Lim

et al.

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(1), P. 95 - 99

Published: Jan. 4, 2024

Abstract Astrocytes are involved in various processes the central nervous system (CNS). As most abundant cell type CNS, astrocytes play an essential role neuronal maintenance and support, synaptic activity, metabolism, amyloid-beta (Aβ) clearance. Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive behavioral impairment. The transformation of diseases, such as AD. Since have functional diversity morphological physiological heterogeneity AD-related might show pathological phenotypes during developing could contribute to AD progression. In this review, we provide overview context AD, highlighting recent findings human mouse

Language: Английский

Citations

39
Microglia-astrocyte crosstalk in the amyloid plaque niche of an Alzheimer’s disease mouse model, as revealed by spatial transcriptomics DOI Creative Commons
Anna Mallach, Magdalena Zielonka, Veerle van Lieshout

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(6), P. 114216 - 114216

Published: May 30, 2024

The amyloid plaque niche is a pivotal hallmark of Alzheimer's disease (AD). Here, we employ two high-resolution spatial transcriptomics (ST) platforms, CosMx and Spatial Enhanced Resolution Omics-sequencing (Stereo-seq), to characterize the transcriptomic alterations, cellular compositions, signaling perturbations in an AD mouse model. We discover heterogeneity composition niches, marked by increase microglial accumulation. profile alterations glial cells vicinity plaques conclude that response consistent across different brain regions, while astrocytic more heterogeneous. Meanwhile, as density niches increases, astrocytes acquire neurotoxic phenotype play key role inducing GABAergic decreasing glutamatergic hippocampal neurons. thus show accumulation microglia around disrupts signaling, turn imbalance neuronal synaptic signaling.

Language: Английский

Citations

21
Trace Elements in Alzheimer’s Disease and Dementia: The Current State of Knowledge DOI Open Access
Magdalena Tyczyńska,

Marta Gędek,

Adam Brachet

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(8), P. 2381 - 2381

Published: April 19, 2024

Changes in trace element concentrations are being wildly considered when it comes to neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. This study aims present the role that elements play central nervous system. Moreover, we reviewed mechanisms involved their neurotoxicity. Low zinc concentrations, well high levels of copper, manganese, iron, activate signalling pathways inflammatory, oxidative nitrosative stress response. Neurodegeneration occurs due association between metals proteins, which is then followed by aggregate formation, mitochondrial disorder, and, ultimately, cell death. In disease, low Zn suppress neurotoxicity induced β-amyloid through selective precipitation aggregation intermediates. High iron manganese cause intracellular α-synuclein, results synaptic dysfunction axonal transport disruption. caused accumulation Fe midbrain dopaminergic nucleus, pathogenesis multiple sclerosis derives from deficiency, leading an imbalance T functions. Aluminium disturbs homeostasis other a rise production oxygen reactive forms, leads cellular Selenium, with plays distinct process ferroptosis. Outlining influence have on oxidoreduction processes crucial recognising pathophysiology diseases may provide possible new methods for both avoidance therapy.

Language: Английский

Citations

18
APP antisense oligonucleotides are effective in rescuing mitochondrial phenotypes in human iPSC‐derived trisomy 21 astrocytes DOI Creative Commons

Srishruthi Thirumalai,

Frederick J. Livesey,

Rickie Patani

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(1)

Published: Jan. 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.

Language: Английский

Citations

2
Astrocytes as a Therapeutic Target in Alzheimer’s Disease–Comprehensive Review and Recent Developments DOI Open Access
Mateo Rodríguez-Giraldo, Rodrigo E. González-Reyes, Sofía Ramírez-Guerrero

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 13630 - 13630

Published: Nov. 7, 2022

Alzheimer’s disease (AD) is a frequent and disabling neurodegenerative disorder, in which astrocytes participate several pathophysiological processes including neuroinflammation, excitotoxicity, oxidative stress lipid metabolism (along with critical role apolipoprotein E function). Current evidence shows that have both neuroprotective neurotoxic effects depending on the stage microenvironmental factors. Furthermore, appear to be affected by presence of amyloid-beta (Aβ), alterations calcium levels, gliotransmission proinflammatory activity via RAGE-NF-κB pathway. In addition, play an important tau clearance Aβ through glymphatic system. this review, we will discuss novel pharmacological non-pharmacological treatments focused as therapeutic targets for AD. These interventions include anti-inflammatory/antioxidant systems, glutamate activity, metabolism, neurovascular coupling system, dysregulation, release peptides affects glial neuronal function. According AD stage, these therapies may benefit either preventing or delaying progression disease.

Language: Английский

Citations

64
Astrocyte biomarkers GFAP and YKL‐40 mediate early Alzheimer's disease progression DOI Creative Commons
Wiesje Pelkmans, Mahnaz Shekari, Anna Brugulat‐Serrat

et al.

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 20(1), P. 483 - 493

Published: Sept. 10, 2023

Abstract INTRODUCTION We studied how biomarkers of reactive astrogliosis mediate the pathogenic cascade in earliest Alzheimer's disease (AD) stages. METHODS performed path analysis on data from 384 cognitively unimpaired individuals ALzheimer and FAmilies (ALFA)+ study using structural equation modeling to quantify relationships between AD pathological cascade. RESULTS Cerebrospinal fluid (CSF) amyloid beta (Aβ) 42/40 was associated with Aβ aggregation positron emission tomography (PET) CSF p‐tau 181 , which turn directly neurofilament light (NfL). Plasma glial fibrillary acidic protein (GFAP) mediated relationship Aβ‐PET, YKL‐40 partly explained association NfL. DISCUSSION Our results suggest that astrogliosis, as indicated by different biomarkers, influences during preclinical stage AD. While plasma GFAP mediates early soluble insoluble Aβ, latter downstream Aβ‐induced tau pathology tau‐induced neuronal injury. Highlights Lower linked higher concentrations. partially Aβ. phosphorylation

Language: Английский

Citations

39
Dysfunctional serotonergic neuron-astrocyte signaling in depressive-like states DOI Creative Commons
Candela González-Arias, Andrea Sánchez-Ruiz, Julio Esparza

et al.

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(9), P. 3856 - 3873

Published: Sept. 1, 2023

Astrocytes play crucial roles in brain homeostasis and are regulatory elements of neuronal synaptic physiology. Astrocytic alterations have been found Major Depressive Disorder (MDD) patients; however, the consequences astrocyte Ca2+ signaling MDD poorly understood. Here, we that corticosterone-treated juvenile mice (Cort-mice) showed altered astrocytic dynamics mPFC both resting conditions during social interactions, line with behavior. Additionally, Cort-mice displayed reduced serotonin (5-HT)-mediated astrocytes, aberrant 5-HT-driven plasticity layer 2/3 neurons. Downregulation naïve animals mimicked deficits Cort-mice. Remarkably, boosting Gq-DREADDS restored to control levels mood cognitive abilities This study highlights important role for homeostatic circuits behavior, but also reveals its potential therapeutic value depressive-like states.

Language: Английский

Citations

39