TY - JOUR
T1 - Modeling the complex pathology of Alzheimer's disease in Drosophila
AU - Fernandez-Funez, Pedro
AU - de Mena, Lorena
AU - Rincon-Limas, Diego E.
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/1/6
Y1 - 2015/1/6
N2 - 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.
AB - 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.
KW - APP
KW - Alzheimer's disease
KW - Aβ42
KW - Disease models
KW - Drosophila
KW - Genetics
KW - Neurodegeneration
KW - Pathology
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=84947037627&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84947037627&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2015.05.013
DO - 10.1016/j.expneurol.2015.05.013
M3 - Article
C2 - 26024860
AN - SCOPUS:84947037627
SN - 0014-4886
VL - 274
SP - 58
EP - 71
JO - Experimental Neurology
JF - Experimental Neurology
ER -