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Transgenic Drosophila models of Alzheimer's disease and tauopathies

Laboratory of Neurogenetics and Pathobiology, Department of Biochemistry and Molecular Biology, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, JHN410, Philadelphia, PA, 19107, USA.
Brain Structure and Function (Impact Factor: 4.57). 12/2009; 214(2-3):245-62. DOI: 10.1007/s00429-009-0234-4
Source: PubMed

ABSTRACT Alzheimer's disease (AD) is the most common form of senile dementia. Aggregation of the amyloid-beta42 peptide (Abeta42) and tau proteins are pathological hallmarks in AD brains. Accumulating evidence suggests that Abeta42 plays a central role in the pathogenesis of AD, and tau acts downstream of Abeta42 as a modulator of the disease progression. Tau pathology is also observed in frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) and other related diseases, so called tauopathies. Although most cases are sporadic, genes associated with familial AD and FTDP-17 have been identified, which led to the development of transgenic animal models. Drosophila has been a powerful genetic model system used in many fields of biology, and recently emerges as a model for human neurodegenerative diseases. In this review, we will summarize key features of transgenic Drosophila models of AD and tauopathies and a number of insights into disease mechanisms as well as therapeutic implications gained from these models.

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    • "These features also make Drosophila an excellent model to study age-related diseases (Mhatre et al., 2013; Iijima-Ando and Iijima, 2010; Moloney et al., 2010; Bonner and Boulianne, 2011; Chakraborty et al., 2011). To date, many Drosophila AD models that exist recapitulate the neuropathology and behavior observed in human AD by overexpressing either mutant forms of APP or Aβ 42 toxic peptides (Greeve et al., 2004; Finelli et al., 2004; Fossgreen et al., 1998; Iijima-Ando et al., 2009; Sofola et al., 2010). However, a majority of these models show AD pathology early, often during stages of their lifecycle where a significant amount of development is still occurring. "
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    • "Furthermore, the γsecretase protein complex mediates OS-induced expression of β-site APP cleaving enzyme I (BACE1) resulting in excessive Aβ production in AD [181]. Remarkably, extensive analysis of the effects and interactions of the AD [182] [183] and PD [184] [185] pathogenic genes in D. melanogaster has shown that mutations in parkin [186] [187], pink-1 [188], α-synuclein [189], Lrrk [190] genes, or overexpression of normal α-synuclein [189] cause death of dopaminergic neurons in Drosophila probably via OS [166, 191–195]. "
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    Oxidative Medicine and Cellular Longevity 04/2012; 2012(163913):163913. DOI:10.1155/2012/163913 · 3.36 Impact Factor
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    • "As a powerful genetic and cell biological system, Drosophila has been used to study AD [6]. Previously, we reported that the ectopic expression of Ab42 in Drosophila neurons induced apoptosis, decreased survivability, and locomotive dysfunction [13]. "
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