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Varderidou, S.

Publications and source records attributed to Varderidou, S..

2 recordsLinked to original sources
bioRxiv2022

Amyotrophic Lateral Sclerosis Proteomic Signature And Treatment With Mesenchymal Stem Cell-derived Extracellular Vesicles

Motor neurons (MNs) derived from human induced pluripotent stem cells (iPSCs) offer a powerful model to study motor neuron diseases, such as amyotrophic lateral sclerosis (ALS). While widely used, our knowledge of the proteomic changes in these models is rather rudimentary. In this study, we conducted a comparative proteomic analysis of iPSC-derived MNs carrying ALS-associated mutations in C9ORF72, TARDBP, or FUS. This revealed both mutation-specific and shared proteomic signatures, unveiling common and divergent disease mechanisms. Using these new insights, we then evaluated the therapeutic potential of extracellular vesicles from mesenchymal stromal/stem cells (MSC-EVs). These experiments showed a functional effect of MSC-EVs in ALS-FUS MNs in vitro and their ability to reverse proteomic changes more generally in MNs with different ALS genetic backgrounds. These findings highlight key molecular pathways involved in ALS at the protein level and support the potential of MSC-EVs as a versatile therapeutic approach. Highlights- This study determines ALS-associated proteomic signatures in iPSC motor neurons (MNs) - Proteomic signatures indicate common and divergent disease mechanisms in MNs - MSC-EV treatment restores neurite growth defects in FUS-ALS MNs - MSC-EVs restore proteomic changes in MNs carrying different ALS mutations

neuroscience↗
bioRxiv2019

Quantitative proteomic alterations of human iPSC-based neuronal development indicate early onset of Rett syndrome.

Rett syndrome (RTT) is a progressive neurodevelopmental disease often caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). The mechanisms by which impaired MeCP2 induces the pathological abnormalities in the brain are not understood. To understand the molecular mechanisms involved in disease, we used an RTT patient induced pluripotent stem cell (iPSC)-based model and applied an in-depth high-resolution quantitative mass spectrometry-based analysis during early stages of neuronal development. Our data provide evidence of proteomic alteration at developmental stages long before the phase that symptoms of RTT syndrome become apparent. Differences in expression profiles became more pronounced from early to late neural stem cell phases, although proteins involved in immunity, metabolic processes and calcium signaling were already affected at initial stages. These results can help development of new biomarkers and therapeutic approaches by selectively target the affected proteins in RTT syndrome.

neuroscience↗