RT info:eu-repo/semantics/article
T1 Isotope-reinforced polyunsaturated fatty acids improve Parkinson’s disease-like phenotype in rats overexpressing α-synuclein
A1 Beal, M. Flint
A1 Chiluwal, Jayandra
A1 Calingasan, Noel Y.
A1 Milne, Ginger L.
A1 Shchepinov, Mikhail S.
A1 Tapias, Victor
AB Lipid peroxidation is a key to a portfolio of neurodegenerative diseases and plays a central role in α-synuclein (α-syn) toxicity, mitochondrial dysfunction and neuronal death, all key processes in the pathogenesis of Parkinson's disease (PD). Polyunsaturated fatty acids (PUFAs) are important constituents of the synaptic and mitochondrial membranes and are often the first molecular targets attacked by reactive oxygen species (ROS). The rate-limiting step of the chain reaction of ROS-initiated PUFAs autoxidation involves hydrogen abstraction at bis-allylic sites, which can be slowed down if hydrogens are replaced with deuteriums. In this study, we show that targeted overexpression of human A53T α-syn using an AAV vector unilaterally in the rat substantia nigra reproduces some of pathological features seen in PD patients. Chronic dietary supplementation with deuterated PUFAs (D-PUFAs), specifically 0.8% D-linoleic and 0.3% H-linolenic, produced significant disease-modifying beneficial effects against α-syn-induced motor deficits, synaptic pathology, oxidative damage, mitochondrial dysfunction, disrupted trafficking along axons, inflammation and DA neuronal loss. These findings support the clinical evaluation of D-PUFAs as a neuroprotective therapy for PD.
YR 2020
FD 2020
LK https://uvadoc.uva.es/handle/10324/63895
UL https://uvadoc.uva.es/handle/10324/63895
LA eng
NO Acta Neuropathologica Communications, Diciembre 2020, vol. 8, n. 1. p. 220
NO Producción Científica
DS UVaDOC
RD 08-ago-2024