title: Biochemical and Behavioral Evaluation of Human MAPT Mutations in Transgenic Drosophila melanogaster.
abstract: Mutations in the human microtubule-associated protein tau (hMAPT) gene including R406W and V337M result in autosomal dominant neurodegenerative disorder. These mutations lead to hyperphosphorylation and aggregation of Tau protein which is a known genetic factor underlying development of Alzheimer's disease (AD). In the present study, transgenic Drosophila models of AD expressing wild-type and mutant forms of hMAPT exhibit a progressive neurodegeneration which was manifested in the form of early death and impairment of cognitive ability. Moreover, they were also found to have significantly decreased activity of neurotransmitter enzymes accompanied by decreased cellular endogenous antioxidant profile. The extent of neurodegeneration, memory impairment, and biochemical profiles was different in the tau transgenic strains which indicate multiple molecular and cellular responses underlie each particular form of hMAPT.
authors.affiliation: Department of Biology, Faculty of Science, University of Zabol, Zabol, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Haddadi
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
authors.forename: Upendra
authors.initials: U
authors.lastname: Nongthomba
authors.affiliation: Department of Studies in Zoology, University of Mysore, Manasagangotri, Mysore, India. rameshuom@gmail.com.
authors.forename: S R
authors.initials: SR
authors.lastname: Ramesh
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal; D002091:Butyrylcholinesterase / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008569:Memory Disorders / Q000235:genetics; D009154:Mutation; D013482:Superoxide Dismutase / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics*
chemical_list: D016875:tau Proteins; D002374:Catalase; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Memory impairment; Neurodegeneration; Oxidative stress; hMAPT