Beneficial effects of n-3 polyunsaturated fatty acids administration in a partial lesion model of Parkinson's disease: The role of glia and NRf2 regulation

2-Hydroxy-Docosahexaenoic Acid Is Converted Into Heneicosapentaenoic Acid via α-Oxidation: Implications for Alzheimer’s Disease Therapy

“…Here, a membrane lipid therapy perspective has been adopted to assess an AD therapy, assuming that the main events triggering the pathophysiology of AD are related to alterations in membrane lipid composition and structure (Escribá et al, 2008. DHA-H, a hydroxylated derivative of DHA, is a drug under pre-clinical development which have widely demonstrated potential therapeutic effects in AD and PD (Fiol-Deroque et al, 2013;Torres et al, 2014Torres et al, , 2015Mohaibes et al, 2017;Hernando et al, 2019). Here, we demonstrate that: (i) DHA-H is metabolically converted into HPA via α-oxidation; (ii) hydroxylation of DHA at the α-carbon confers resistance to its incorporation into other lipids and promotes its accumulation as a free fatty acid in cell membranes; (iii) DHA-H and DHA accumulate distinctly in cells and they regulate cellular lipid composition; (iv) hydroxylation of DHA at the α-carbon hinders its drug incorporation into cultured cells; (v) mouse administration of DHA-H leads to an increase in plasma HPA levels over and above those of DHA-H; (vi) brain DHA levels are not significantly modified by DHA-H administration; (vii) only HPA, and not DHA-H, is detected in the DHA-H-treated mouse brain; and (viii) HPA brain levels are closely related to improved spatial memory in 5xFAD mice.…”

“…Hence, the use of DHA-H appears likely to preserve neuronal density, as seen in cell models where DHA-H prevents the neuronal death induced by β-amyloid oligomers or by NMDA (N-Methyl-D-Aspartate) and calcium (excitotoxicity) (Torres et al, 2014(Torres et al, , 2015. Finally, DHA-H also has beneficial effects in an animal model of Parkinson's disease, where it prevented oxidative stress and dopaminergic neuron death (Hernando et al, 2019).…”

The Implications for Cells of the Lipid Switches Driven by Protein–Membrane Interactions and the Development of Membrane Lipid Therapy

“…Such signals appear to be especially relevant in the context of cell proliferation. Thus, either the increase in cell proliferation caused by tumor alterations or decreased proliferation related to neurodegeneration (e.g., AD or Parkinson's disease (PD)) have been related to membrane lipid modifications [8,12,15,88,89].…”

Protection from the Pathogenesis of Neurodegenerative Disorders, including Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, Huntington’s Disease, and Parkinson’s Diseases, through the Mitigation of Reactive Oxygen Species

“…In addition, magnesium, ino sitol, choline, B 1 , iso lavones, and anthocyanins may help prevent the development of AD [91]. In addition, dietary omega-3 fatty acids are also known to improve the functioning of the brain in a similar manner [92,93]. A study comprising 815 participants between the ages of 65 and 94 found a 60% lower risk of developing AD in those who consumed ish at least once per week [94].…”