Angelova P.R.,University College London |
Horrocks M.H.,University of Cambridge |
Klenerman D.,University of Cambridge |
Gandhi S.,University College London |
And 2 more authors.
Journal of Neurochemistry | Year: 2015
Parkinson's disease is the second most common neurodegenerative disease and its pathogenesis is closely associated with oxidative stress. Deposition of aggregated α-synuclein (α-Syn) occurs in familial and sporadic forms of Parkinson's disease. Here, we studied the effect of oligomeric α-Syn on one of the major markers of oxidative stress, lipid peroxidation, in primary co-cultures of neurons and astrocytes. We found that oligomeric but not monomeric α-Syn significantly increases the rate of production of reactive oxygen species, subsequently inducing lipid peroxidation in both neurons and astrocytes. Pre-incubation of cells with isotope-reinforced polyunsaturated fatty acids (D-PUFAs) completely prevented the effect of oligomeric α-Syn on lipid peroxidation. Inhibition of lipid peroxidation with D-PUFAs further protected cells from cell death induced by oligomeric α-Syn. Thus, lipid peroxidation induced by misfolding of α-Syn may play an important role in the cellular mechanism of neuronal cell loss in Parkinson's disease. © 2015 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of The International Society for Neurochemistry.
Lamberson C.R.,Vanderbilt University |
Xu L.,Vanderbilt University |
Muchalski H.,Vanderbilt University |
Montenegro-Burke J.R.,Vanderbilt University |
And 6 more authors.
Journal of the American Chemical Society | Year: 2014
Substitution of -CD2- at the reactive centers of linoleic and linolenic acids reduces the rate of abstraction of D by a tocopheryl radical by as much as 36-fold, compared to the abstraction of H from a corresponding -CH2- center. This H atom transfer reaction is the rate-determining step in the tocopherol-mediated peroxidation of lipids in human low-density lipoproteins, a process that has been linked to coronary artery disease. The unanticipated large kinetic isotope effects reported here for the tocopherol-mediated oxidation of linoleic and linolenic acids and esters suggests that tunneling makes this process favorable. © 2013 American Chemical Society.
Retrotope | Date: 2012-04-24
Some aspects of the invention provide for a method of treating Alzheimers Disease, Mild Cognitive Impairment, Frontotemperal Dementia, Amyotrophic Lateral Sclerosis and/or Multiple Sclerosis using polyunsaturated fatty acids which are modified in certain positions to attenuate oxidative damage by Reactive Oxygen Species (ROS) and/or suppress the rate of formation of reactive products and toxic compounds.
Retrotope | Date: 2014-11-24
Retrotope | Date: 2012-04-24
Some aspects of the invention provide for a method of treating hepatic disorders, lipidemias and cardiac-related risk factors using polyunsaturated fatty acids which are modified in certain positions to attenuate oxidative damage by Reactive Oxygen Species (ROS) and/or suppress the rate of formation of reactive products and toxic compounds.