Tuesday, January 19, 2016

Wednesday, January 13, 2016

Report of a fly model of ADHD

Zhang Q, Du G, John V, Kapahi P, Bredesen DE. Alzheimer's Model Develops Early ADHD Syndrome. J Neurol Neurophysiol. 2015;6(6):1-6. PMID: 26753104.

From the abstract: "We describe the first invertebrate model of attention deficit hyperactivity disorder (ADHD) that reproduces its major features, including hyperactivity, male predominance, marked exacerbation by simple carbohydrates, ... This model may offer new insight into ADHD pathogenesis and treatment. Furthermore, these findings are of particular interest in light of the recent epidemiological evidence showing that patients with dementia have a high frequency of antecedent ADHD symptoms."

Tuesday, January 5, 2016

Fly model used in study of mutations in LRRK2 associated with Parkinson's disease

Mortiboys H, Furmston R, Bronstad G, Aasly J, Elliott C, Bandmann O. UDCA [ursodeoxycholic acid] exerts beneficial effect on mitochondrial dysfunction in LRRK2(G2019S) carriers and in vivo. Neurology. 2015 Sep 8;85(10):846-52. PMID: 26253449; PMCID: PMC4560055.

From the abstract: "OBJECTIVE: To further characterize mitochondrial dysfunction in LRRK2(G2019S) mutant Parkinson disease (PD) patient tissue (M-LRRK2(G2019S)), determine whether ursodeoxycholic acid (UDCA) also exerts a beneficial effect on mitochondrial dysfunction in nonmanifesting LRRK2(G2019S) mutation carriers (NM-LRRK2(G2019S)), and assess UDCA for its beneficial effect on neuronal dysfunction in vivo. ... CONCLUSION: ... The beneficial effect of UDCA on mitochondrial function in both NM-LRRK2(G2019S) and M-LRRK2(G2019S) as well as on the function of dopaminergic neurons expressing LRRK2(G2019S) suggests that UDCA is a promising drug for future neuroprotective trials."

See also: Greenamyre JT, Sanders LH, Gasser T. Fruit flies, bile acids, and Parkinson disease: a mitochondrial connection? Neurology. 2015 Sep 8;85(10):838-9. PMID: 26253445.

Fly natural population GWAS study contributes new knowledge relevant to retinitis pigmentosa

Chow CY, Kelsey KJ, Wolfner MF, Clark AG. Candidate genetic modifiers of retinitis pigmentosa identified by exploiting natural variation in Drosophila. Hum Mol Genet. 2015 Dec 11. pii: ddv502. PMID: 26662796.

From the abstract: "Individuals carrying the same pathogenic mutation can present with a broad range of disease outcomes. While some of this variation arises from environmental factors, it is increasingly recognized that the background genetic variation of each individual can have a profound effect on the expressivity of a pathogenic mutation. In order to understand this background effect on disease-causing mutations, studies need to be performed across a wide range of backgrounds. Recent advancements in model organism biology allow us to test mutations across genetically diverse backgrounds ... we used the Drosophila Genetic Reference Panel, a collection of ∼200 wild-derived strains, to test the variability of the retinal phenotype of the Rh1G69D Drosophila model of retinitis pigmentosa (RP). We found that the Rh1G69D retinal phenotype is quite a variable quantitative phenotype. To identify the genes driving this extensive phenotypic variation, we performed a genome-wide association study. We identified 106 candidate genes, including 14 high-priority candidates. ... These candidate modifiers provide new avenues of inquiry that may reveal new RP disease mechanisms and therapies."

New fly models of FIG4-related diseases including Charcot-Marie-Tooth

Bharadwaj R, Cunningham KM, Zhang K, Lloyd TE. FIG4 regulates lysosome membrane homeostasis independent of phosphatase function. Hum Mol Genet. 2015 Dec 11. pii: ddv505. PMID: 26662798.

From the abstract: "FIG4 is a phosphoinositide phosphatase that is mutated in several diseases including Charcot-Marie-Tooth Disease 4J (CMT4J) and Yunis-Varon syndrome (YVS). To investigate the mechanism of disease pathogenesis, we generated Drosophila models of FIG4-related diseases. Fig4 null mutant animals are viable but exhibit marked enlargement of the lysosomal compartment in muscle cells and neurons, accompanied by an age-related decline in flight ability. Transgenic animals expressing Drosophila Fig4 missense mutations corresponding to human pathogenic mutations can partially rescue lysosomal expansion phenotypes, consistent with these mutations causing decreased FIG4 function. Interestingly, Fig4 mutations predicted to inactivate FIG4 phosphatase activity rescue lysosome expansion phenotypes, and mutations in the phosphoinositide (3) phosphate kinase Fab1 that performs the reverse enzymatic reaction also causes a lysosome expansion phenotype. ... These data show that FIG4 plays a critical noncatalytic function in maintaining lysosomal membrane homeostasis, and that this function is disrupted by mutations that cause CMT4J and YVS."

FlyRNAi: Fly cell RNAi screen identifies "first in vivo med...

FlyRNAi: Fly cell RNAi screen identifies "first in vivo med...: Congrats to Taneli and the rest of the team on this report of a screen performed at the DRSC ! Helenius IT, Haake RJ, Kwon YJ, Hu JA, Kru...

Fly model of Parkinsons Disease used to study effects of extract from folk remedy plant Withania somnifera