linoleic-acid and Huntington-Disease

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease which has no effective treatment and is characterized by psychiatric disorders, motor alterations, and dementia, with the cognitive deficits representing a devastating aspect of the disorder. Oxidative stress and elevated levels of lipid peroxidation (LPO) products are found in mouse models and patients with HD, suggesting that strategies to reduce LPO may be beneficial in HD. In contrast with traditional antioxidants, substituting hydrogen with deuterium at bis-allylic sites in polyunsaturated fatty acids (D-PUFA) decreases the rate-limiting initiation step of PUFA autoxidation, a strategy that has shown benefits in other neurodegenerative diseases. Here, we investigated the effect of D-PUFA treatment in a knock-in mouse model of HD (Q140) which presents motor deficits and neuropathology from a few months of age, and progressive cognitive decline. Q140 knock-in mice were fed a diet containing either D- or H-PUFAs for 5 months starting at 1 month of age. D-PUFA treatment significantly decreased F

Topics: Animals; Body Weight; Cognitive Dysfunction; Deuterium; Dietary Supplements; Disease Models, Animal; Fatty Acids, Unsaturated; Female; Huntingtin Protein; Huntington Disease; Linoleic Acid; Lipid Peroxidation; Male; Mice, Transgenic; Motor Activity

Phospholipid class, peak profile of each phospholipid class, loosely bound fatty acids, covalently (tightly) bound fatty acids of the erythrocyte membranes, and plasma fatty acids were investigated using high-performance liquid chromatography in six patients with chorea-acanthocytosis and 14 age- and sex-matched normal control subjects. Additionally, six patients with Huntington's disease were included as disease control subjects in the study of covalently bound fatty acids. Study of covalently (tightly) bound fatty acids in erythrocyte membrane proteins after alkaline hydrolysis, hitherto undescribed in chorea-acanthocytosis, revealed that palmitic acid (C16:0) was significantly increased and stearic acid (C18:0) was decreased in the patients with chorea-acanthocytosis. Analyses for total covalently bound fatty acids disclosed that palmitic and docosahexaenoic (C22:6) acids were increased and stearic acid was decreased in chorea-acanthocytosis. Phospholipid class (phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and phosphatidylserine) and peak profile of each phospholipid class from the erythrocyte membranes did not differ between the patients with chorea-acanthocytosis and the control subjects. Of the loosely bound fatty acids, linoleic acid (C18:2) was significantly decreased in those with chorea-acanthocytosis, which seemed to be nonspecific.

Topics: Acanthocytes; Adult; Chorea; Erythrocyte Membrane; Fatty Acids; Female; Humans; Huntington Disease; Linoleic Acid; Linoleic Acids; Male; Membrane Lipids; Membrane Proteins; Middle Aged; Palmitic Acid; Palmitic Acids; Phospholipids; Stearic Acids; Syndrome