文章基本信息

标题：Engineered Hsp70 chaperones prevent Aβ42-induced memory impairments in a Drosophila model of Alzheimer’s disease
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作者：Alfonso Martín-Peña ; Diego E. Rincón-Limas ; Pedro Fernandez-Fúnez 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：9915
DOI：10.1038/s41598-018-28341-w
语种：English
出版社：Springer Nature
摘要：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-β42 (Aβ42) 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 Aβ42 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 Aβ42. Both Hsp70 isoforms significantly improved memory performance of flies expressing Aβ42, irrespective of their age or the level of Aβ42 load. Using olfactory classical conditioning, we established a Drosophila model of AD based on Aβ42 neurotoxicity and monitored memory decline through aging. The onset of the memory impairment observed was proportional to the cumulative level of Aβ42 in the Drosophila brain. These data support the use of this Drosophila model of AD to further investigate molecules with a protective activity against Aβ42-induced memory loss, contributing to the development of palliative therapies for AD.