Lipids are major constituents of living cells, as they are important structural components of cell membranes. Polyunsaturated fatty acids (PUFAs) are long-chain fatty acids (18 carbons or more) that contain two or more double bonds. Depending on the location of the last double bond, PUFAs are classified into families such as omega-3 (last double bond on the third carbon starting from the methyl group) and omega-6 (last double bond on the sixth carbon from the methyl group). Contrary to fatty acids that can be synthesized in the human body, some of them cannot be produced de novo and must be incorporated through diet [1]. The latter are called essential fatty acids, and they include omega-6 family precursor linoleic acid (18:2n-6) and omega-3 family precursor α-linolenic acid (LNA, 18:3n-3). By a cascade of alternating desaturase and elongase enzymatic reactions, which are common to both families, longer PUFAs are biosynthesized from their respective precursors [2]. PUFAs are mainly found esterified within glycerophospholipids present in cell membranes at the sn-1 and sn-2 positions. Glycerophospholipids are grouped by the structure of their polar head group on the sn-3 position. Their amphiphilic nature (one hydrophilic head group and two hydrophobic fatty acids) confers fluidity and selective permeability to the membranes they constitute [3,4]. They are also precursors for signaling metabolites, including eicosanoids, growth hormones, and regulators, and they participate in important physiological processes, such as anti-inflammatory or pro-inflammatory responses [5,6,7,8].

There is a specific enrichment of essential fatty acids in human tissues, notably in the retina, brain, and heart. Contrary to arachidonic acid (ArA, 20:4n-6), which is the major PUFA of human tissues, docosahexaenoic acid (DHA, 22:6n-3) is the most prominent fatty acid in the brain, where it is considered functionally essential [9,10]. DHA concentration is especially high in neurons where it facilitates development and synaptic functions [11], with a special interest in human brain evolution [12]. A proper balance between omega-6 and omega-3 supplementation during pregnancy and infancy is required for correct neural development [13,14,15]. Along with aging, a decrease in long-chain PUFA levels in the brain has been observed, especially for DHA levels [16,17,18]. These deficiencies are correlated to a cognitive decline in normal aging but might be even more detrimental in pathological aging. In Alzheimer’s disease, decreases in PUFAs, particularly in essential fatty acids such as DHA, have been observed [19,20,21]. These results hint at a possible correlation between neurodegenerative diseases and cerebral DHA deficiency.

DHA has many beneficial properties, especially for cerebral diseases such as Alzheimer’s disease, that were covered in numerous reviews [22,23,24,25,26]. These include pro-neurogenic, anti-oxidative, anti-inflammatory, and anti-apoptotic properties. These potent neuroprotective effects might be partly due to the conversion of DHA into active secondary metabolites such as protectins, including protectin DX [27], resolvins, and maresins [28]. DHA can also be transformed into N-Docosahexaenoylethanolamide, an endocannabinoid-like lipid mediator that has been named synaptamide due to its capacity to induce synaptogenesis, neurogenesis, and neurite outgrowth [29,30,31]. Due to its enrichment in double bonds, DHA can also provide fluidity to cell membranes [3,32,33]. As increasing its accretion into the brain through esterification into structured phospholipids improves cognitive functions in healthy brains [34], it might also heighten its neuroprotection against neuronal death.

2. DHA-Containing Phospholipid for the Treatment of Alzheimer’s Disease

3. Potential Therapy to Other Neurological Diseases

4. AceDoPC as a Potential Antioxidant and Neurogenesis Inducer