Engineered Hsp70 chaperones prevent A?42-induced memory impairments in a Drosophila model of Alzheimer's disease.

ABSTRACT: Proteinopathies constitute a group of diseases in which certain proteins are abnormally folded leading to aggregation and eventual cell failure. Most neurodegenerative diseases belong to protein misfolding disorders and, among them, Alzheimer's disease (AD) is the most prevalent. AD is characterized by accumulation of the amyloid-?42 (A?42) peptide in the extracellular space. Hence, we genetically engineered a molecular chaperone that was selectively delivered to this cellular location. It has been reported that the heat shock protein 70 (Hsp70) binds A?42 preventing self-aggregation. Here, we employed two isoforms of the Hsp70, cytosolic and extracellular, to evaluate their potential protective effect against the memory decline triggered by extracellular deposition of A?42. Both Hsp70 isoforms significantly improved memory performance of flies expressing A?42, irrespective of their age or the level of A?42 load. Using olfactory classical conditioning, we established a Drosophila model of AD based on A?42 neurotoxicity and monitored memory decline through aging. The onset of the memory impairment observed was proportional to the cumulative level of A?42 in the Drosophila brain. These data support the use of this Drosophila model of AD to further investigate molecules with a protective activity against A?42-induced memory loss, contributing to the development of palliative therapies for AD.

SUBMITTER: Martin-Pena A 

PROVIDER: S-EPMC6028656 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature