Alzheimer's Disease, β-Amyloid Peptides, and Ubiquitin-Proteasome System: Nutritherapeutic Insights

Alzheimer's disease - an age-related neurodegenerative disorder leading to progressive cognitive impairment - is characterized by an intracerebral accumulation of soluble β-amyloid (Aβ) oligomers, followed by the appearance of abnormally ubiquitinylated neurofibrillary tangles - a process associated with a chronic inflammation. The systematic presence of ubiquitinylated inclusions reflects a decrease in the proteasome activity due to (and contributing to) the presence of Aβ oligomers - a central dysfunction in the etiology of the disease.

The involvement of the ubiquitin-proteasome system opens new therapeutic perspectives for both prevention and treatment. In particular, the potential for synergistic strategies combining diet-derived proteasome activators, immunoproteasome inhibitors, and modulators of Aβ peptide aggregation to prevent, delay or even reverse disease progression over time is currently arousing growing interest.

From that perspective, and in light of the recent advances in the understanding of the key molecular and cellular mechanisms underlying Alzheimer's disease pathogenesis, the present review highlights the mechanisms of action and the preventive and therapeutic potential of some diet-derived bioactive compounds and other natural substances of interest. This article is a translated, updated, and expanded version of an article originally published in French in Médecine/Sciences, August/September 2023 (https://doi.org/10.1051/medsci/2023094).