Alzheimer's disease, amyloid-b peptides and ubiquitin-proteasome system: Therapeutic perspectives

The Alzheimer's disease - an age-related neurodegenerative disorder leading to a 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.