Extracellular vesicles in ALS patients' cells: Characterization and study of their modulation upon pharmacological treatment

Bueso De Barrio, Jesus Alejandro

4. term

Nanotechnology, Master

2022

Amyotrofisk lateral sklerose (ALS) er en neurodegenerativ sygdom, der skader de øvre og nedre motorneuroner, som styrer viljestyrede bevægelser. Årsagerne er ukendte, og der findes ingen kur. Fordi ALS varierer meget mellem patienter, er det særligt udfordrende at udvikle lægemidler. I dette projekt brugte vi blodafledte patient-cellmodeller, som genskaber abnormiteter i TAR DNA-bindende protein 43 (TDP-43), et protein der ofte er forstyrret i neuroner ved ALS. Vi undersøgte ekstracellulære vesikler (EV'er)—små membranbundne pakker, som celler frigiver—fra lymfoblastiske ALS-modeller og fra kontrol-lymfoblaster. Vi målte deres størrelse, koncentration og indhold af ALS-relaterede biomolekyler. For at kunne påvise disse vesikler mærkede vi dem med kvanteprik-nanopartikler (QD), som fungerer som lysstærke, nanoskopiske markører. Vi analyserede også, hvordan hæmning af casein kinase 1δ (CK-1δ), et enzym, påvirker disse EV'er.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that damages the upper and lower motor neurons controlling voluntary movement. Its causes remain unknown and there is no cure. Because ALS varies greatly between patients, developing medicines is especially challenging. In this project, we used blood-derived patient cell models that reproduce abnormalities of TAR DNA-binding protein 43 (TDP-43), a protein often disrupted in neurons in ALS. We examined extracellular vesicles (EVs)—tiny membrane-bound packages released by cells—from lymphoblastic ALS models and from control lymphoblasts. We measured their size, concentration, and the content of ALS-related biomolecules. To detect these vesicles, we labeled them with quantum dot (QD) nanoparticles, which serve as bright, nanoscale tags. We also analyzed how inhibiting casein kinase 1δ (CK-1δ), an enzyme, affects these EVs.

[This abstract was generated with the help of AI]

ALS ; SALS ; TDP-43 ; Quantum Dot Nanoparticles ; miRNA detection ; neuroscience ; lymphoblastic model ; extracellular vesicles ; EVs ; exosomes ; ectosomes ; CD63 labelling ; FRET ; NTA ; TEM ; AFM ; CK-1δ

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