Knockdown of APPL mimics transgenic Aβ induced neurodegenerative phenotypes in Drosophila.
A variety of Drosophila mutant lines have been established as potential disease-models to study various disease mechanisms including human neurodegenerative diseases like Alzheimer's disease (AD), Huntington's disease (HD) and Parkinson's disease (PD). The evolutionary conservation of APP (Amyloid Precursor Protein) and APPL (Amyloid Precursor Protein-Like) and the comparable detrimental effects caused by their metabolic products strongly implies the conservation of their normal physiological functions. In view of this milieu, a comparative analysis on the pattern of neurodegenerative phenotypes between Drosophila APPL-RNAi line and transgenic Drosophila line expressing eye tissue specific human Aβ (Amyloid beta) was undertaken. Our results clearly show that Drosophila APPL-RNAi largely mimics transgenic Aβ in various phenotypes which include eye degeneration, reduced longevity and motor neuron deficit functions, etc. The ultra-structural morphological pattern of eye degeneration was confirmed by scanning electron microscopy. Further, a comparative study on longevity and motor behaviour between Aβ expressing and APPL knockdown lines revealed similar kind of behavioural deficit and longevity phenotypes. Therefore, it is suggested that APPL-knockdown approach can be used as an alternative approach to study neurodegenerative diseases in the fly model. To the best of our knowledge this is the first report showing comparable phenotypes between APPL and Aβ in AD model of Drosophila.
Cancer and Neurobiology Laboratory, Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
Sandeep Kumar
SK
Singh
Cancer and Neurobiology Laboratory, Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
Saurabh
S
Srivastav
Cancer and Neurobiology Laboratory, Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
Amarish Kumar
AK
Yadav
Cancer and Neurobiology Laboratory, Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India. Electronic address: skrishna@bhu.ac.in.
Saripella
S
Srikrishna
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics*; D005123:Eye / Q000648:ultrastructure; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009043:Motor Activity; D009046:Motor Neurons / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics; D010641:Phenotype; D016019:Survival Analysis
C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; C066839:Appl protein, Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins
APP; APPL-RNAi; Alzheimer's disease; Drosophila; Eye degeneration; Longevity; Motor neuron function; SEM