Novel extracellular vesicle release pathway facilitated by toxic superoxide dismutase 1 oligomers

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

Published: April 10, 2025

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease resulting in paralysis and death within three to five years. Mutations over forty different proteins have been linked ALS, leading controversy whether ALS one or many diseases with similar phenotype. Cu,Zn superoxide dismutase 1 (SOD1) are only found 2-3% of cases, yet misfolded SOD1 both sporadic (sALS) familial (fALS) patients. Yet, mutations TDP-43 FUS increase the level on extracellular vesicles (EVs). Additionally, small EVs isolated from patient samples caused cell wild type motor neurons myotubules. The toxicity protein alterations led theory that responsible for spread ALS. We hypothesize previously-identified toxic trimeric spreading altering other ALS-related proteins, linking them common mechanism. To test our hypothesis, we isolate neuron-like cells expressing trimer stabilizing perform sandwich enzyme-linked immunoassay (ELISA) (CD9 capture antibody) quantify 17 decrease stabilization. identify which EV release pathway being affected by utilizing endocytosis exocytosis inhibitors, determine if any specific EV-related altered establish VAPB, VCP, Stathmin-2 between ALS-associated multiple pathways, including Caveolae pathway, suggesting novel hybrid present

Language: Английский

Programmable control of spatial transcriptome in live cells and neurons

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: May 21, 2025

Language: Английский