RT Journal Article
T1 Interactions between Angiotensin Type-1 Antagonists, Statins, and ROCK Inhibitors in a Rat Model of L-DOPA-Induced Dyskinesia
A1 López López, Andrea
A1 Valenzuela Limiñana, Rita
A1 Rodríguez Pérez, Ana Isabel
A1 Guerra Seijas, María Josefa Natividad
A1 Labandeira García, José Luis
A1 Muñoz Patiño, Ana María
K1 L-DOPA
K1 Parkinson
K1 Rho-Kinase
K1 Angiotensin
K1 Brain cholesterol
K1 Dyskinesia
K1 Fasudil
K1 Neuroinflammation
K1 Oxidative stress
K1 Simvastatin.
AB Statins have been proposed for L-DOPA-induced dyskinesia (LID) treatment. Statin anti-dyskinetic effects were related to the inhibition of the Ras-ERK pathway. However, the mechanisms responsible for the anti-LID effect are unclear. Changes in cholesterol homeostasis and oxidative stress- and inflammation-related mechanisms such as angiotensin II and Rho-kinase (ROCK) inhibition may be involved. The nigra and striatum of dyskinetic rats showed increased levels of cholesterol, ROCK, and the inflammatory marker IL-1β, which were reduced by the angiotensin type-1 receptor (AT1) antagonist candesartan, simvastatin, and the ROCK inhibitor fasudil. As observed for LID, angiotensin II-induced, via AT1, increased levels of cholesterol and ROCK in the rat nigra and striatum. In cultured dopaminergic neurons, angiotensin II increased cholesterol biosynthesis and cholesterol efflux without changes in cholesterol uptake. In astrocytes, angiotensin induced an increase in cholesterol uptake, decrease in biosynthesis, and no change in cholesterol efflux, suggesting a neuronal accumulation of cholesterol that is reduced via transfer to astrocytes. Our data suggest mutual interactions between angiotensin/AT1, cholesterol, and ROCK pathways in LID, which are attenuated by the corresponding inhibitors. Interestingly, these three drugs have also been suggested as neuroprotective treatments against Parkinson's disease. Therefore, they may reduce dyskinesia and the progression of the disease using common mechanisms.
PB MDPI
YR 2023
FD 2023-07-19
LK https://hdl.handle.net/10347/38914
UL https://hdl.handle.net/10347/38914
LA eng
NO Lopez-Lopez, A., Valenzuela, R., Rodriguez-Perez, A. I., Guerra, M. J., Labandeira-Garcia, J. L., & Muñoz, A. (2023). Interactions between Angiotensin Type-1 Antagonists, Statins, and ROCK Inhibitors in a Rat Model of L-DOPA-Induced Dyskinesia. Antioxidants (Basel, Switzerland), 12(7), 1454. https://doi.org/10.3390/antiox12071454
DS Minerva
RD 23 may 2026