Simvastatin attenuates disease phenotypes in human induced pluripotent stem cell models of familial Parkinson's disease through RhoA inhibition
Background: Statins have gained increasing interest for their potential therapeutic effect in Parkinson's disease (PD). Beyond their cholesterol-lowering effect, statins decrease synthesis of isoprenoids, which is believed to account for their pleiotropic effects. Isoprenylation is important for proper membrane localization and function of the Rho GTPases, including RhoA. RhoA signalling has…
Parkinson's disease is increasingly linked to vascular dysfunction, but the role of vascular pathology in disease progression is not well understood. Researchers created a 3D model of brain tissue that included engineered neurospheroids and a self-assembled vascular network to better capture the neurovascular interface. By introducing preformed fibrils of α-synuclein into the engineered blood vessels, they were able to study the vascular contribution to Parkinson's disease pathology.
The results showed that exposing the vascular network to α-synuclein fibrils led to endothelial barrier disruption, vascular leakage, inflammation, and vascular regression. Importantly, this vascular damage also triggered intraneuronal aggregation of α-synuclein within the neurospheroids, indicating that vascular dysfunction may help expose neural tissue to pathogenic α-synuclein.
This new modeling approach provides a versatile platform for investigating how vascular issues can contribute to the progression of neurodegenerative diseases like Parkinson's.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
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