The aim of this study was to evaluate the fatty acids, tocopherols, squalene, sterols and phenolic antioxidants in three types of argan oil (Moroccan food, Moroccan aesthetic and a French commercial variety) along with a basic comparison with extra virgin olive and sunflower oil. The fatty acid profiles in the argan oils were very similar, with oleic acid (43%) and linoleic acid (36%) and their respective monoacylglycerols predominating. The major vitamer identified was -tocopherol with a mean of 483+/-11 mg/kg, in contrast to -tocopherol, which is the major vitamer in olive (190+/-1 mg/kg) and sunflower oil (532+/-6 mg/kg). The squalene content of the argan oils was very similar with a mean of 313+/-4 mg/100 g, which is lower than that of the olive oil (499 mg/100 g) but significantly higher than in the sunflower oil (6 mg/100 g). In contrast to olive and sunflower oils in which -sitosterol is predominant, the major sterols detected in the argan oils were schottenol (mean 147+/-10 mg/kg) and spinasterol (mean 122+/-10 mg/kg). The only phenolic compounds other than the tocopherol vitamers which could be readily detected and quantitated were vanillic, syringic and ferulic (probably conjugated to glucose) acids along with tyrosol. In contrast to the extra virgin olive oil (793 mg/kg), the concentration of total phenolic compounds is extremely low (<5.0 mg/kg). Nevertheless, argan oil with its high content of the vitamer -tocopherol, squalene and oleic acid is likely to enhance the cancer prevention effects of the Moroccan diet.

No abstract

Recent data have revealed that soluble oligomeric forms of amyloid peptide (Abeta) may be the proximate effectors of the neuronal injury and death occurring in Alzheimer's disease (AD). However, the molecular mechanisms associated with the neuronal cell death induced by the nonfibrillar Abeta remain to be elucidated. In this study, we investigated the role of the cytosolic Ca2+-dependent phospholipase A2 (cPLA2), and its associated metabolic pathway, i.e., the arachidonic acid (AA) cascade, in the apoptotic cell death induced by soluble oligomers of Abeta. The treatment of rat cortical neurons with low concentrations of soluble Abeta(1-40) or Abeta(1-42) peptide resulted in an early calcium-dependent release of AA associated with a transient relocalization of cPLA2. Both cPLA2 antisense oligonucleotides and a selective inhibitor of cPLA2 activity abolished the release of AA from neurons and also protected cells against apoptosis induced by Abeta. Furthermore, inhibitors of the PKC, p38, and MEK/ERK pathways that are involved in cPLA2 phosphorylation and activation reduced Abeta-induced cell death. Finally, we demonstrate that inhibitors of cyclooxygenase-2 reduced the Abeta-induced cell death by 55%. Our studies suggest a novel neuronal response of soluble oligomers of Abeta, which occurs through a cPLA2 signaling cascade and an AA-dependent death pathway. This may prove to be crucial in AD processes and could provide important targets for drug development.

A growing body of evidence supports the notion that soluble oligomers of amyloid-b (Ab) peptide interact with the neuronal plasma membrane, leading to cell injury and inducing deathsignalling pathways that could account for the increased neurodegeneration occurring in Alzheimer's disease (AD). Docosahexaenoic acid (DHA, C22:6, n-3) is an essential polyunsaturated fatty acid in the CNS and has been shown in several epidemiological and in vivo studies to have protective effects against AD and cognitive alterations. However, the molecular mechanisms involved remain unknown. We hypothesized that DHA enrichment of plasma membranes could protect neurones from apoptosis induced by soluble Ab oligomers. DHA pre-treatment was observed to significantly increase neuronal survival upon Ab treatment by preventing cytoskeleton perturbations, caspase activation and apoptosis, as well as by promoting extracellular signal-related kinase (ERK)-related survival pathways. These data suggest that DHA enrichment probably induces changes in neuronal membrane properties with functional outcomes, thereby increasing protection from soluble Ab oligomers. Such neuroprotective effects could be of major interest in the prevention of AD and other neurodegenerative diseases.

A growing body of evidence supports the notion that soluble oligomeric forms of the amyloid ␤-peptide (A␤) may be the proximate effectors of neuronal injuries and death in the early stages of Alzheimer disease. However, the molecular mechanisms associated with neuronal apoptosis induced by soluble A␤ remain to be elucidated. We recently demonstrated the involvement of an early reactive oxygen species-dependent perturbation of the microtubule network (Sponne, I., Fifre, A., Drouet, B., Klein, C., Koziel, V., Pincon-Raymond, M., Olivier, J.-L., Chambaz, J., and Pillot, T. Microtubules are polymers of ␣-and ␤-tubulin dimers that mediate many functions in neurons, including organelle transport and cell shape establishment and maintenance as well as axonal elongation and growth cone steering in neurons. The polymerization, stabilization, and dynamic properties of microtubules are influenced by interactions with microtubule-associated proteins (MAPs).3 Members of this protein family are classified by size: high molecular mass proteins (MAP1A, MAP1B, MAP2a, and MAP2b) and intermediate molecular mass proteins (MAP2c, MAP2d, and tau) (1-3). Numerous studies have shown that neuronal apoptotic cell death involves alterations of the microtubule network consequent to calpain and effector caspase activation (4, 5). These calcium-dependent proteases are responsible for the degradation and turnover of a broad repertoire of MAP substrates, some of which they share, such as ␣II-spectrin and tau, and some of which are specific, as is the case of calpain-degraded MAP1B and MAP2.Intraneuronal neurofibrillary tangles (NFTs) are one of the histopathological hallmarks in brains of patients diagnosed with Alzheimer disease (AD), a progressive dementia that manifests primarily as a profound inability to form new memories. These NFTs are composed of hyperphosphorylated tau organized into paired helical filaments (PHFs) (6). In addition, AD is also associated with the presence of extracellular senile plaques (7) formed as a consequence of the gradual accumulation and aggregation of the amyloid ␤-peptide (A␤) into fibrils (8). Despite evidence that A␤ represents a key factor in AD (9), the nature of the toxic form of A␤ involved early in AD pathology remains to be determined. The issue of which pool (soluble or aggregated) of A␤ in brain is more deleterious in the early stages of AD is still controversial (10). However, clinicopathological hallmarks of AD correlate far better with the soluble pool of A␤ (11,12). Moreover, several studies in transgenic mice have indicated that specific cognitive deficits, neurodegeneration, and synaptic loss might occur before any histologically detectable formation of senile plaques (13,14). So, in reports from our group (15-18) and others (19,20), attention has been paid to the soluble oligomeric forms of A␤ as the principal mediators of neurodegeneration in the early stages of AD development (10, 19 -23).Increasing evidence suggests that the selective neuronal cell death in AD involves activation of caspa...