Modeling the complex pathology of Alzheimer's disease in Drosophila.

Abstract:

:Alzheimer's disease (AD) is the leading cause of dementia and the most common neurodegenerative disorder. AD is mostly a sporadic disorder and its main risk factor is age, but mutations in three genes that promote the accumulation of the amyloid-β (Aβ42) peptide revealed the critical role of amyloid precursor protein (APP) processing in AD. Neurofibrillary tangles enriched in tau are the other pathological hallmark of AD, but the lack of causative tau mutations still puzzles researchers. Here, we describe the contribution of a powerful invertebrate model, the fruit fly Drosophila melanogaster, to uncover the function and pathogenesis of human APP, Aβ42, and tau. APP and tau participate in many complex cellular processes, although their main function is microtubule stabilization and the to-and-fro transport of axonal vesicles. Additionally, expression of secreted Aβ42 induces prominent neuronal death in Drosophila, a critical feature of AD, making this model a popular choice for identifying intrinsic and extrinsic factors mediating Aβ42 neurotoxicity. Overall, Drosophila has made significant contributions to better understand the complex pathology of AD, although additional insight can be expected from combining multiple transgenes, performing genome-wide loss-of-function screens, and testing anti-tau therapies alone or in combination with Aβ42.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Fernandez-Funez P,de Mena L,Rincon-Limas DE

doi

10.1016/j.expneurol.2015.05.013

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

58-71

issue

Pt A

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(15)00169-7

journal_volume

274

pub_type

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