Application of Multiomics Approach to Investigate the Therapeutic Potentials of Stem Cell-derived Extracellular Vesicle Subpopulations for Alzheimer's Disease DOI Creative Commons
Morteza Abyadeh, Alaattin Kaya

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 14, 2024

Alzheimer's disease (AD) presents a complex interplay of molecular alterations, yet understanding its pathogenesis remains challenge. In this study, we delved into the intricate landscape proteome and transcriptome changes in AD brains compared to healthy controls, examining 788 brain samples revealing common alterations at both protein mRNA levels. Moreover, our analysis revealed distinct protein-level aberrant energy metabolism pathways that were not evident level. This suggests expression could provide deeper representation pathogenesis. Subsequently, using comparative proteomic approach, explored therapeutic potential mesenchymal stem cell-derived extracellular vehicles (EVs), isolated through various methods, mitigating AD-associated Our particular EV-subtype can be utilized for compensating dysregulated mitochondrial proteostasis brain. By network biology approaches, further regulators key proteins. Overall, study illuminates significance identifies promise specific EV subpopulation with reduced pro-inflammatory cargo enriched proteins target proteostasis.

Language: Английский

Proteomic profiling of mesenchymal stem cell‐derived extracellular vesicles: Impact of isolation methods on protein cargo DOI Creative Commons
Morteza Abyadeh, Shahab Mirshahvaladi, Sara Assar Kashani

et al.

Journal of Extracellular Biology, Journal Year: 2024, Volume and Issue: 3(6)

Published: June 1, 2024

Abstract Extracellular vesicles (EVs) are nanosized with a lipid bilayer that secreted by cells and play critical role in cell‐to‐cell communication. Despite the promising reports regarding their diagnostic therapeutic potential, utilization of EVs clinical setting is limited due to insufficient information about cargo lack standardization isolation analysis methods. Considering protein cargos as key contributors potency, we conducted tandem mass tag (TMT) quantitative proteomics three subpopulations mesenchymal stem cell (MSC)‐derived obtained through different techniques: ultracentrifugation (UC), high‐speed centrifugation (HS), on sucrose cushion (SU). Subsequently, checked EV marker expression, size distribution, morphological characterization, followed bioinformatic analysis. The proteome results revealed these exhibit distinct molecular functional characteristics. choice method impacts isolated isolating EVs. Specifically, (HS) exhibited higher abundance ribosomal mitochondrial proteins. Functional apoptosis assays comparing mitochondria methods HS‐EVs, but not other EVs, induced early cancer cells. On hand, using (SU) (UC) demonstrated proteins primarily involved immune response, cell‐cell interactions extracellular matrix interactions. Our analyses unveil notable disparities associated biological functions among subpopulations, underscoring importance meticulously selecting resultant based intended application.

Language: Английский

Citations

12
Proteomics profiling of extracellular vesicle for identification of potential biomarkers in Alzheimer's disease: A comprehensive review DOI
Jinjin Pei, Chella Perumal Palanisamy,

Selvaraj Jayaraman

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102359 - 102359

Published: May 29, 2024

Language: Английский

Citations

8
The Role of Extracellular Vesicles in Metabolic Diseases DOI Creative Commons
Carlos González-Blanco,

Sarai Iglesias-Fortes,

Ángela Cristina Lockwood

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(5), P. 992 - 992

Published: April 30, 2024

Extracellular vesicles represent a group of structures with the capacity to communicate different cells and organs. This complex network interactions can regulate multiple physiological processes in organism. Very importantly, these be altered during appearance diseases including cancer, metabolic diseases, etc. In addition, extracellular transport cargoes, altering initiation disease, driving progression, or even accelerating pathogenesis. Then, we have explored implication alterations such as pancreatic diabetes its complications non-alcoholic fatty liver disease. Finally, more detail communication between pancreas. summary, very efficient system for among tissues permit an biomarkers well being involved extracellular-vesicle-mediated molecules, serving potential therapy diseases.

Language: Английский

Citations

5
Multiomics from Alzheimer’s Brains and Mesenchymal Stem Cell-Derived Extracellular Vesicles Identifies Therapeutic Potential of Specific Subpopulations to Target Mitochondrial Proteostasis DOI Creative Commons
Morteza Abyadeh, Alaattin Kaya

Journal of Central Nervous System Disease, Journal Year: 2025, Volume and Issue: 17

Published: April 1, 2025

Background Alzheimer’s disease (AD) is characterized by complex molecular alterations that complicate its pathogenesis and contribute to the lack of effective treatments. Mesenchymal stem cell-derived extracellular vesicles (EVs) have shown promise in AD models, but results across different EV subpopulations remain inconsistent. Objectives This study investigates proteomic transcriptomic data from publicly available postmortem brain datasets identify changes at both gene protein levels. These findings are then compared with proteomes various subpopulations, differing size distribution, determine most promising subtype for compensating degeneration AD. Design We conducted a comprehensive analysis 788 samples, including 481 cases 307 healthy controls, examining mRNA levels uncover AD-associated changes. were potential therapeutic candidates. Methods A multi-omics approach was employed, integrating analysis, miRNA transcription factor profiling, protein-protein network construction, hub identification, enrichment analyses. aimed explore brains pinpoint relevant intervention. Results identified common cAMP signaling pathway coagulation cascade Distinct energy metabolism observed level not level. specific subtype, broader distribution obtained through high-speed centrifugation, as capable dysregulated mitochondrial proteostasis brains. Network biology analyses further highlighted regulators key proteins within this subtype. Conclusion underscores critical role identifies subpopulation, enriched targeting proteostasis, strategy

Language: Английский

Citations

0
Extracellular vesicles as therapeutic modulators of neuroinflammation in Alzheimer’s disease: a focus on signaling mechanisms DOI Creative Commons

Jianping Han,

Xue Zhang, Lixing Kang

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: April 25, 2025

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) plaques and tau tangles, which contribute significantly to neuroinflammation, central driver pathogenesis. The activation microglia astrocytes, coupled with complex interactions between Aβ pathologies innate immune response, leads cascade inflammatory events. This process triggers release pro-inflammatory cytokines chemokines, exacerbating neuronal damage fostering cycle chronic inflammation that accelerates neurodegeneration. Key signaling pathways, such as nuclear factor-kappa B (NF-κB), Janus kinase/signal transducer activator transcription (JAK/STAT), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein (PI3K/Akt), are involved in regulating production these mediators, offering potential therapeutic targets for AD. Recently, extracellular vesicles (EVs) have emerged promising tool AD therapy, due their ability cross blood-brain barrier (BBB) deliver agents. Despite challenges standardizing EV-based therapies ensuring safety, EVs offer novel approach modulating neuroinflammation promoting neuroregeneration. review aims highlight intricate relationship emerging role therapeutics advancing treatment strategies.

Language: Английский

Citations

0
New insights into extracellular vesicles of clinical and therapeutic interest using proteomic mass spectrometry approaches DOI

Cindy Nix,

Marianne Fillet

TrAC Trends in Analytical Chemistry, Journal Year: 2024, Volume and Issue: 178, P. 117823 - 117823

Published: June 19, 2024

Language: Английский

Citations

1
Application of Multiomics Approach to Investigate the Therapeutic Potentials of Stem Cell-derived Extracellular Vesicle Subpopulations for Alzheimer's Disease DOI Creative Commons
Morteza Abyadeh, Alaattin Kaya

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 14, 2024

Alzheimer's disease (AD) presents a complex interplay of molecular alterations, yet understanding its pathogenesis remains challenge. In this study, we delved into the intricate landscape proteome and transcriptome changes in AD brains compared to healthy controls, examining 788 brain samples revealing common alterations at both protein mRNA levels. Moreover, our analysis revealed distinct protein-level aberrant energy metabolism pathways that were not evident level. This suggests expression could provide deeper representation pathogenesis. Subsequently, using comparative proteomic approach, explored therapeutic potential mesenchymal stem cell-derived extracellular vehicles (EVs), isolated through various methods, mitigating AD-associated Our particular EV-subtype can be utilized for compensating dysregulated mitochondrial proteostasis brain. By network biology approaches, further regulators key proteins. Overall, study illuminates significance identifies promise specific EV subpopulation with reduced pro-inflammatory cargo enriched proteins target proteostasis.

Language: Английский

Citations

0