linoleic-acid and Neurodegenerative-Diseases

The well-known health effects of the long-chain, marine omega-3 (n-3) fatty acids (FAs) has led to a growing interest in the prognostic value that blood levels of these FAs might have vis-à-vis cardiovascular and neurocognitive diseases. The measurement and expression of n-3 FA levels is not straight-forward, however, and a wide variety of means of expression of n-3 FA status have been used in research and clinical medicine. This has led to considerable confusion as to what "optimal" n-3 FA status is. The n-6:n-3 ratio has enjoyed relatively widespread use, but this apparently simple metric has both theoretical and practical difficulties that have contributed to misunderstandings in this field. Just as the once-popular polyunsaturated:saturated FA ratio has largely disappeared from the nutritional and medical literature, it may be time to replace the n-6:n-3 ratio with a newer metric that focuses on the primary deficiency in Western diets - the lack of eicosapentaenoic and docosahexaenoic acids (EPA and DHA). The Omega-3 Index (red blood cell EPA+DHA) has much to recommend it in this regard.

Topics: Arachidonic Acid; Biomarkers; Cardiovascular Diseases; Dietary Fats; Docosahexaenoic Acids; Eicosapentaenoic Acid; Erythrocytes; Humans; Linoleic Acid; Neurodegenerative Diseases; Reference Values

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer's disease. The principal pathological feature of PD is the progressive loss of dopaminergic neurons in the ventral midbrain. This pathology involves several cellular alterations: oxidative stress, mitochondrial dysfunction, loss of proteostasis, and autophagy impairment. Moreover, in recent years, lipid metabolism alterations have become relevant in PD pathogeny. The modification of lipid metabolism has become a possible way to treat the disease. Because of this, we analyzed the effect and possible mechanism of action of linoleic acid (LA) on an SH-SY5Y PD cell line model and a PD mouse model, both induced by 6-hydroxydopamine (6-OHDA) treatment. The results show that LA acts as a potent neuroprotective and anti-inflammatory agent in these PD models. We also observed that LA stimulates the biogenesis of lipid droplets and improves the autophagy/lipophagy flux, which resulted in an antioxidant effect in the in vitro PD model. In summary, we confirmed the neuroprotective effect of LA in vitro and in vivo against PD. We also obtained some clues about the novel neuroprotective mechanism of LA against PD through the regulation of lipid droplet dynamics.

Topics: Animals; Autophagy; Cell Line, Tumor; Humans; Linoleic Acid; Lipid Droplets; Mice; Neuroblastoma; Neurodegenerative Diseases; Oxidopamine; Parkinson Disease

Hempseed is rich in polyunsaturated fatty acids (PUFAs), which have potential as therapeutic compounds for the treatment of neurodegenerative and cardiovascular disease. However, the effect of hempseed meal (HSM) intake on the animal models of these diseases has yet to be elucidated. In this study, we assessed the effects of the intake of HSM and PUFAs on oxidative stress, cytotoxicity and neurological phenotypes, and cholesterol uptake, using Drosophila models. HSM intake was shown to reduce H(2)O(2) toxicity markedly, indicating that HSM exerts a profound antioxidant effect. Meanwhile, intake of HSM, as well as linoleic or linolenic acids (major PUFA components of HSM) was shown to ameliorate Aβ42-induced eye degeneration, thus suggesting that these compounds exert a protective effect against Aβ42 cytotoxicity. On the contrary, locomotion and longevity in the Parkinson's disease model and eye degeneration in the Huntington's disease model were unaffected by HSM feeding. Additionally, intake of HSM or linoleic acid was shown to reduce cholesterol uptake significantly. Moreover, linoleic acid intake has been shown to delay pupariation, and cholesterol feeding rescued the linoleic acid-induced larval growth delay, thereby indicating that linoleic acid acts antagonistically with cholesterol during larval growth. In conclusion, our results indicate that HSM and linoleic acid exert inhibitory effects on both Aβ42 cytotoxicity and cholesterol uptake, and are potential candidates for the treatment of Alzheimer's disease and cardiovascular disease.

Topics: alpha-Linolenic Acid; Amyloid beta-Peptides; Animals; Animals, Genetically Modified; Antioxidants; Cannabis; Cardiovascular Diseases; Cholesterol; Compound Eye, Arthropod; Drosophila melanogaster; Hydrogen Peroxide; Hypercholesterolemia; Linoleic Acid; Lipid Metabolism; Motor Activity; Neurodegenerative Diseases; Peptide Fragments; Seeds