Monday, March 28, 2016

Fly models used to validate association of proteins with Alzheimers disease

Minjarez B, Calderón-González KG, Rustarazo ML, Herrera-Aguirre ME, Labra-Barrios ML, Rincon-Limas DE, Del Pino MM, Mena R, Luna-Arias JP. Identification of proteins that are differentially expressed in brains with Alzheimer's disease using iTRAQ labeling and tandem mass spectrometry. J Proteomics. 2016 Mar 21. PMID: 27012543.

From the abstract: "Alzheimer's disease is one of the leading causes of dementia in the elderly. It is considered the result of complex events involving both genetic and environmental factors. To gain further insights into this complexity, we quantitatively analyzed the proteome of cortex region of brains from patients diagnosed with Alzheimer's disease, using a bottom-up proteomics approach. ... We used Drosophila to validate some of the hits ... We manipulated their homolog genes in Drosophila models of Aβ- and Tau-induced pathology. We found proteins that can either modify Aβ toxicity, Tau toxicity or both, suggesting specific interactions with different pathways. This approach illustrates the potential of Drosophila to validate hits after MS studies and suggest that model organisms should be included in the pipeline to identify relevant targets for Alzheimer's disease. ... With this approach, Sideroflexin and Phosphoglucomutase-1 were identified as novel proteins connected with Alzheimer's disease."

Thursday, March 24, 2016

Drosophila studies help implicate ALFY gene in human primary microcephaly

Kadir R, Harel T, Markus B, Perez Y, Bakhrat A, Cohen I, Volodarsky M, Feintsein-Linial M, Chervinski E, Zlotogora J, Sivan S, Birnbaum RY, Abdu U, Shalev S, Birk OS. ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size. PLoS Genet. 2016 Mar 23;12(3):e1005919. PMID: 27008544.

From the abstract: "Primary microcephaly is a congenital neurodevelopmental disorder of reduced head circumference and brain volume ... We now show ... that a dominant mutation in ALFY, encoding an autophagy scaffold protein, causes human primary microcephaly. We demonstrate the dominant effect of the mutation in drosophila: transgenic flies harboring the human mutant allele display small brain volume, recapitulating the disease phenotype ..."