Abstract
Alzheimer’s disease (AD) is a major public health concern in all developped countries. Although the precise cause of AD is still unknown, a growing body of evidence supports the notion that soluble oligomers of amyloid b-peptide (Aβ) may be the proximate effectors of synaptic injuries and neuronal death in the early stages of AD. AD patients display lower levels of docosahexaenoic acid (DHA, C22:6; n-3) in plasma and brain tissues as compared to control subjects of same age. Furthermore, epidemiological studies suggest that high DHA intake might have protective properties against neurodegenerative diseases. These observations are supported by in vivo studies showing that DHA-rich diets limit the synaptic loss and cognitive defects induced by Aβ peptide. Although the molecular basis underlying these neuroprotective effects remains unknown, several mechanisms have been proposed such as (i) regulation of the expression of potentially protective genes, (ii) activation of antiinflammatory pathways, (iii) modulation of functional properties of the synaptic membranes along with changes in their physicochemical and structural features. We recently demonstrated that DHA protects neurons from soluble Aβ oligomer-induced apoptosis. Indeed, DHA pretreatment was observed to significantly increase neuronal survival upon Aβ treatment by preventing cytoskeleton perturbations, caspase activation and apoptosis, as well as by promoting ERK-related survival pathways. These data suggest that DHA enrichment most likely induces changes in neuronal membrane properties with functional outcomes, thereby increasing protection from soluble Aβ oligomers. Such neuroprotective effects could be of major interest in the prevention of AD and other neurodegenerative diseases.
Highlights
Alzheimer’s disease (AD) is a progressive dementia that manifests in early stages primarily as a profound inability to form new memories
Several epidemiological and experimental data suggest that DHA intake and enrichment in neuronal membranes could provide a substantial protective effect against these devastating pathologies, which undoubtedly represents one of the most promising preventive approaches to develop with the aim to prevent or to delay the onset of AD
Tify the proteins and domains in the plasma membrane that could act as protective sensors able to induce the antiapoptotic response triggered by DHA enrichment in neurons
Summary
Alzheimer’s disease (AD) is a progressive dementia that manifests in early stages primarily as a profound inability to form new memories. Studies from our group have demonstrated that exposure of cells to soluble Ab could lead to neuronal apoptosis following oxidative stress, pro-inflammatory signals and cytoskeleton perturbation [3, 4] Such neurotoxicity strongly suggests that soluble Ab oligomers could be the proximate effectors of the neuronal injury and death occurring in the precocious stages of AD [2]. Docosahexaenoic acid (DHA, C22:6D4,7,10,13,16,19; n-3) represents the longest and the most unsaturated fatty acid (FA) commonly found in biological systems and is mainly present in fish and algae It is the major n-3 PUFA constituent of the neuronal membranes in the grey matter of the cerebral cortex and in retinal photoreceptor cells [6]. ALA approach with high-density microarrays revealed changes in the expression of brain
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