Integrative Human Genetic and Cellular Analysis of the Pathophysiological Roles of AnxA2 in Alzheimer’s Disease DOI Creative Commons
Lianmeng Ye, Jiazheng Zhao, Zhengpan Xiao

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1274 - 1274

Published: Oct. 21, 2024

Alzheimer's disease (AD) is an intractable and progressive neurodegenerative disease. Amyloid beta (Aβ) aggregation the hallmark of AD. Aβ induces neurotoxicity through a variety mechanisms, including interacting with membrane receptors to alter downstream signaling, damaging cellular or organelle membranes, interfering protein degradation synthesis, inducing excessive immune-inflammatory response, all which lead neuronal death other pathological changes associated In this study, we extracted gene expression profiles from GSE5281 GSE97760 microarray datasets in GEO (Gene Expression Omnibus) database, as well Human Gene Database. We identified differentially expressed genes brain tissues AD patients healthy persons. Through GO, KEGG, ROC analyses, annexin A2 (AnxA2) was putative target gene. Notably, accumulating evidence suggests that intracellular AnxA2 key regulator various biological processes, endocytosis, transmembrane transport, neuroinflammation, apoptosis. Thus, conducted series cell biology experiments explore function The results indicate knockdown primarily affects oxidative phosphorylation, cycle, AD, processing endoplasmic reticulum, SNARE interactions vesicular autophagy. SH-SY5Y cells secreting Aβ42, exacerbated Aβ42-induced cytotoxicity, death, ROS levels, senescence, altered reduced ATP suggesting its critical role mitochondrial maintenance. also inhibitory effect Aβ42 on migration. overexpression inflammatory response induced by while absence increased pro-inflammatory decreased anti-inflammatory responses. Furthermore, facilitated apoptosis These indicated potential pathophysiological roles

Language: Английский

Small Heat Shock Proteins: Protein Aggregation Amelioration and Neuro- and Age-Protective Roles DOI Open Access
Tahani H. Albinhassan,

Bothina Mohammed Alharbi,

Entissar S. AlSuhaibani

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1525 - 1525

Published: Feb. 11, 2025

Protein misfolding, aggregation, and aberrant aggregate accumulation play a central role in neurodegenerative disease progression. The proteotoxic factors also govern the aging process to large extent. Molecular chaperones modulate proteostasis thereby impact aberrant-protein-induced proteotoxicity. These have diverse functional spectrum, including nascent protein folding, misfolded sequestration, refolding, or degradation. Small heat shock proteins (sHsps) possess an ATP-independent chaperone-like activity that prevents aggregation by keeping target folding-competent state be refolded ATP-dependent chaperones. Due their near-universal upregulation presence sites of stress like diseased brains, sHsps were considered pathological. However, gene knockdown overexpression studies established protective functions. This review provides updated overview sHsp amelioration highlights evidence for modulation disease-related aging.

Language: Английский

Citations

1
Characterization of isolated human astrocytes from aging brain DOI Creative Commons
Geidy E. Serrano, Sidra Aslam, Jessica E. Walker

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

ABSTRACT Astrocytes have multiple crucial roles, including maintaining brain homeostasis and synaptic function, performing phagocytic clearance responding to injury repair. It has been suggested that astrocyte performance is progressively impaired with aging, leading imbalances in the brain’s internal milieu eventually impact neuronal function leads neurodegeneration. Until now most of evidence astrocytic dysfunction aging come from experiments done whole tissue homogenates, astrocytes collected by laser capture or cell cultures derived animal models lines. In this study we used postmortem-derived cells sorted anti-GFAP antibodies compare unbiased, whole-transcriptomes human control, older non-impaired individuals subjects different neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s (ADD) progressive supranuclear palsy (PSP). We found hundreds dysregulated genes between control astrocytes. addition, identified numerous shared these common disorders are similarly dysregulated; particular, UBC a gene for ubiquitin, which protein integral cellular critically important regulating outcomes proteins under stress, was upregulated PSP, PD, ADD when compared control.

Language: Английский

Citations

0
Hypergraph-based analysis of weighted gene co-expression hypernetwork DOI Creative Commons

Libing Bai,

Zongjin Li, Chunyang Tang

et al.

Frontiers in Genetics, Journal Year: 2025, Volume and Issue: 16

Published: April 4, 2025

Background With the rapid advancement of gene sequencing technologies, Traditional weighted co-expression network analysis (WGCNA), which relies on pairwise relationships, struggles to capture higher-order interactions and exhibits low computational efficiency when handling large, complex datasets. Methods To overcome these challenges, we propose a novel Weighted Gene Co-expression Hypernetwork Analysis (WGCHNA) based hypergraph, where genes are modeled as nodes samples hyperedges. By calculating hypergraph Laplacian matrix, WGCHNA generates topological overlap matrix for module identification through hierarchical clustering. Results four expression datasets show that outperforms WGCNA in functional enrichment. identifies biologically relevant modules with greater complexity, particularly processes like neuronal energy metabolism linked Alzheimer’s disease. Additionally, enrichment uncovers more comprehensive pathway hierarchies, revealing potential regulatory relationships targets. Conclusion effectively addresses WGCNA’s limitations, providing superior accuracy detecting deeper insights disease research, making it powerful tool analyzing biological systems.

Language: Английский

Citations

0
Characterization of Isolated Human Astrocytes from Aging Brain DOI Open Access
Geidy E. Serrano, Sidra Aslam, Jessica E. Walker

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3416 - 3416

Published: April 5, 2025

Astrocytes have multiple crucial roles, including maintaining brain homeostasis and synaptic function, performing phagocytic clearance, responding to injury repair. It has been suggested that astrocyte performance is progressively impaired with aging, leading imbalances in the brain's internal milieu eventually impact neuronal function lead neurodegeneration. Until now, most evidence of astrocytic dysfunction aging come from experiments done whole tissue homogenates, astrocytes collected by laser capture, or cell cultures derived animal models lines. In this study, we used postmortem-derived cells sorted anti-GFAP antibodies compare unbiased, whole-transcriptomes human control, older non-impaired individuals subjects different neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's (ADD), progressive supranuclear palsy (PSP). We found hundreds dysregulated genes between control astrocytes. addition, identified numerous shared these common disorders are similarly dysregulated; particular, UBC a gene for ubiquitin, which protein integral cellular critically important regulating outcomes proteins under stress, was upregulated PSP, PD, ADD when compared control.

Language: Английский

Citations

0
Integrative Human Genetic and Cellular Analysis of the Pathophysiological Roles of AnxA2 in Alzheimer’s Disease DOI Creative Commons
Lianmeng Ye, Jiazheng Zhao, Zhengpan Xiao

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1274 - 1274

Published: Oct. 21, 2024

Alzheimer's disease (AD) is an intractable and progressive neurodegenerative disease. Amyloid beta (Aβ) aggregation the hallmark of AD. Aβ induces neurotoxicity through a variety mechanisms, including interacting with membrane receptors to alter downstream signaling, damaging cellular or organelle membranes, interfering protein degradation synthesis, inducing excessive immune-inflammatory response, all which lead neuronal death other pathological changes associated In this study, we extracted gene expression profiles from GSE5281 GSE97760 microarray datasets in GEO (Gene Expression Omnibus) database, as well Human Gene Database. We identified differentially expressed genes brain tissues AD patients healthy persons. Through GO, KEGG, ROC analyses, annexin A2 (AnxA2) was putative target gene. Notably, accumulating evidence suggests that intracellular AnxA2 key regulator various biological processes, endocytosis, transmembrane transport, neuroinflammation, apoptosis. Thus, conducted series cell biology experiments explore function The results indicate knockdown primarily affects oxidative phosphorylation, cycle, AD, processing endoplasmic reticulum, SNARE interactions vesicular autophagy. SH-SY5Y cells secreting Aβ42, exacerbated Aβ42-induced cytotoxicity, death, ROS levels, senescence, altered reduced ATP suggesting its critical role mitochondrial maintenance. also inhibitory effect Aβ42 on migration. overexpression inflammatory response induced by while absence increased pro-inflammatory decreased anti-inflammatory responses. Furthermore, facilitated apoptosis These indicated potential pathophysiological roles

Language: Английский

Citations

2