SNCA triplication disrupts proteostasis and extracellular architecture prior to neurodegeneration in human midbrain organoids - PubMed
5 days ago
- #Parkinson's disease
- #midbrain organoids
- #SNCA triplication
- SNCA triplication in human midbrain organoids disrupts proteostasis and extracellular matrix architecture before neurodegeneration.
- Early changes include alterations in protein synthesis and stress response signaling pathways.
- Proteomic and transcriptomic analyses show modulation of neuronal pathways and extracellular matrix components.
- Ribosome profiling indicates selective translational buffering for neuronal and matrix-related transcripts.
- Imaging reveals increased pericellular and interstitial matrix structures, particularly around TH+ neurons.
- Findings suggest early molecular disruptions precede overt neurodegenerative changes in synucleinopathies.