Effects of DHA (omega-3 fatty acid) and estradiol on amyloid β-peptide regulation in the brain.

Autor: Majou D; ACTIA, 149, rue de Bercy, 75595 Paris Cedex 12, France. Electronic address: d.majou@actia-asso.eu., Dermenghem AL; ACTIA, 149, rue de Bercy, 75595 Paris Cedex 12, France.
Jazyk: angličtina
Zdroj: Brain research [Brain Res] 2024 Jan 15; Vol. 1823, pp. 148681. Date of Electronic Publication: 2023 Nov 20.
DOI: 10.1016/j.brainres.2023.148681
Abstrakt: In the early stages of sporadic Alzheimer's disease (SAD), there is a strong correlation between memory impairment and cortical levels of soluble amyloid-β peptide oligomers (Aβ). It has become clear that Aβ disrupt glutamatergic synaptic function, which can in turn lead to the characteristic cognitive deficits of SAD, but the actual pathways are still not well understood. This opinion article describes the pathogenic mechanisms underlying cerebral amyloidosis. These mechanisms are dependent on the amyloid precursor protein and concern the synthesis of Aβ peptides with competition between the non-amyloidogenic pathway and the amyloidogenic pathway (i.e. a competition between the ADAM10 and BACE1 enzymes), on the one hand, and the various processes of Aβ residue clearance, on the other hand. This clearance mobilizes both endopeptidases (NEP, and IDE) and removal transporters across the blood-brain barrier (LRP1, ABCB1, and RAGE). Lipidated ApoE also plays a major role in all processes. The disturbance of these pathways induces an accumulation of Aβ. The description of the mechanisms reveals two key molecules in particular: (i) free estradiol, which has genomic and non-genomic action, and (ii) free DHA as a preferential ligand of PPARα-RXRα and PPARɣ-RXRα heterodimers. DHA and free estradiol are also self-regulating, and act in synergy. When a certain level of chronic DHA and free estradiol deficiency is reached, a permanent imbalance is established in the central nervous system. The consequences of these deficits are revealed in particular by the presence of Aβ peptide deposits, as well as other markers of the etiology of SAD.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
Externí odkaz: