Ott S, Dziadulewicz N, Crowther DC. Iron is a specific cofactor for distinct oxidation- and aggregation-dependent Aβ toxicity mechanisms. Dis Model Mech. 2015 Apr 23. pii: dmm.019042. PMID: 26035384.
From the abstract: "Metals including iron are present at high concentrations in amyloid plaques in patients with Alzheimer's disease where they are also thought to be co-factors in generating oxidative stress and modulating amyloid formation. In this study we present data from several Drosophila models of neurodegenerative proteinopathies indicating that the interaction between iron and Aβ is specific and is not seen for other aggregation-prone polypeptides. ... Understanding how Aβ mediates neurotoxic effects in vivo will help us better target pathological pathways using aggregation-blockers and metal-modifying agents."
Monday, June 15, 2015
Wednesday, June 3, 2015
Review looks at contributions of Drosophila research related to Fragile X syndrome and discusses discordance
Weisz ED, Monyak RE, Jongens TA. Deciphering Discord: How Drosophila research has enhanced our understanding of the importance of FMRP in different spatial and temporal contexts. Exp Neurol. 2015 May 27. pii: S0014-4886(15)30001-7. PMID: 26026973.
From the abstract: "Fragile X Syndrome (FXS) is the most common heritable form of intellectual impairment as well as the leading monogenetic cause of autism. ... Research efforts in Drosophila melanogaster have revealed key insights into the mechanistic underpinnings of FXS. While much remains unknown, it is increasingly apparent that FXS involves a myriad of spatial and temporally specific alterations in cellular function. Consequently, the literature is filled with numerous discordant findings. Researchers and clinicians alike must be cognizant of this dissonance, as it will likely be important for the design of preclinical studies to assess the efficacy of therapeutic strategies to improve the lives of FXS patients."
From the abstract: "Fragile X Syndrome (FXS) is the most common heritable form of intellectual impairment as well as the leading monogenetic cause of autism. ... Research efforts in Drosophila melanogaster have revealed key insights into the mechanistic underpinnings of FXS. While much remains unknown, it is increasingly apparent that FXS involves a myriad of spatial and temporally specific alterations in cellular function. Consequently, the literature is filled with numerous discordant findings. Researchers and clinicians alike must be cognizant of this dissonance, as it will likely be important for the design of preclinical studies to assess the efficacy of therapeutic strategies to improve the lives of FXS patients."
New fly model related to mitochondrial diseases
Holmbeck MA, Donner JR, Villa-Cuesta E, Rand DM. A Drosophila model for mito-nuclear diseases generated by an incompatible tRNA-tRNA synthetase interaction. Dis Model Mech. 2015 May 5. pii: dmm.019323. PMID: 26035388.
From the abstract: "... Because mutations in mitochondrial tRNATyr are associated with exercise intolerance in humans, this mitochondrial-nuclear introgression model in Drosophila provides a means to dissect the molecular basis of these, and other mitochondrial diseases that are a consequence of the joint genetic architecture of mitochondrial function."
From the abstract: "... Because mutations in mitochondrial tRNATyr are associated with exercise intolerance in humans, this mitochondrial-nuclear introgression model in Drosophila provides a means to dissect the molecular basis of these, and other mitochondrial diseases that are a consequence of the joint genetic architecture of mitochondrial function."
Fly study related to Parkinson's disease places Clu in context of PINK1, Parkin and mitochondrial quality control
Sen A, Kalvakuri S, Bodmer R, Cox RT. Clueless, a protein required for mitochondrial function, interacts with the PINK1-Parkin complex in Drosophila. Dis Model Mech. 2015 Jun 1;8(6):577-589. PMID: 26035866.
From the abstract: "Loss of mitochondrial function often leads to neurodegeneration and is thought to be one of the underlying causes ... we show that clu also genetically interacts with PINK1, and our epistasis analysis places clu downstream of PINK1 and upstream of park. ... Clu forms a complex with PINK1 and Park ... Lack of Clu causes PINK1 and Park to interact with each other, and clu mutants have decreased mitochondrial protein levels ... these results suggest that Clu directly modulates mitochondrial function, and that Clu's function contributes to the PINK1-Park pathway of mitochondrial quality control."
Note: clu has been conserved--the orthologous human protein appears to be CLUH.
From the abstract: "Loss of mitochondrial function often leads to neurodegeneration and is thought to be one of the underlying causes ... we show that clu also genetically interacts with PINK1, and our epistasis analysis places clu downstream of PINK1 and upstream of park. ... Clu forms a complex with PINK1 and Park ... Lack of Clu causes PINK1 and Park to interact with each other, and clu mutants have decreased mitochondrial protein levels ... these results suggest that Clu directly modulates mitochondrial function, and that Clu's function contributes to the PINK1-Park pathway of mitochondrial quality control."
Note: clu has been conserved--the orthologous human protein appears to be CLUH.
Review--modeling Alzheimers disease in flies
Fernandez-Funez P, de Mena L, Rincon-Limas DE. Modeling the complex pathology of Alzheimer's disease in Drosophila. Exp Neurol. 2015 May 27. pii: S0014-4886(15)00169-7. PMID: 26024860.
New fly model related to Adult T-cell leukemia/lymphoma (ATLL)
Shirinian M, Kambris Z, Hamadeh L, Grabbe C, Journo C, Mahieux R, Bazarbachi A. A transgenic Drosophila melanogaster model to study Human T-Lymphotropic Virus oncoprotein Tax-1-driven transformation in vivo. J Virol. 2015 May 20. pii: JVI.00918-15. PMID: 25995252.
From the abstract: "HTLV-1-induced adult T-cell leukemia/lymphoma is an aggressive malignancy. ... We describe transgenic Drosophila models expressing Tax in the compound eye and plasmatocytes. ... Tax-1 but not Tax-2 induces ommatidia perturbation and increased plasmatocyte proliferation ... validating this new in vivo model."
From the abstract: "HTLV-1-induced adult T-cell leukemia/lymphoma is an aggressive malignancy. ... We describe transgenic Drosophila models expressing Tax in the compound eye and plasmatocytes. ... Tax-1 but not Tax-2 induces ommatidia perturbation and increased plasmatocyte proliferation ... validating this new in vivo model."
Fly study suggest links between mitochondrial iron transport and Friedreich's ataxia
Navarro JA, Botella JA, Metzendorf C, Lind MI, Schneuwly S. Mitoferrin modulates iron toxicity in a Drosophila model of Friedreich׳s ataxia. Free Radic Biol Med. 2015 Apr 2. pii: S0891-5849(15)00126-4. PMID: 25841783.
From the abstract: "Friedreich׳s ataxia is the most important recessive ataxia in the Caucasian population. Loss of frataxin expression affects the production of iron-sulfur clusters and, therefore, mitochondrial energy production. One of the pathological consequences is an increase of iron transport into the mitochondrial compartment leading to a toxic accumulation of reactive iron. ... frataxin-deficient flies were hypersensitive toward dietary iron and developed an iron-dependent decay of mitochondrial functions. ... mitoferrin downregulation improved many of the frataxin-deficient conditions ... whereas mitoferrin overexpression exacerbated most of them. ... demonstrates the crucial role of mitoferrin dysfunction in the etiology of Friedreich׳s ataxia and provides evidence that impairment of mitochondrial iron transport could be an effective treatment of the disease."
From the abstract: "Friedreich׳s ataxia is the most important recessive ataxia in the Caucasian population. Loss of frataxin expression affects the production of iron-sulfur clusters and, therefore, mitochondrial energy production. One of the pathological consequences is an increase of iron transport into the mitochondrial compartment leading to a toxic accumulation of reactive iron. ... frataxin-deficient flies were hypersensitive toward dietary iron and developed an iron-dependent decay of mitochondrial functions. ... mitoferrin downregulation improved many of the frataxin-deficient conditions ... whereas mitoferrin overexpression exacerbated most of them. ... demonstrates the crucial role of mitoferrin dysfunction in the etiology of Friedreich׳s ataxia and provides evidence that impairment of mitochondrial iron transport could be an effective treatment of the disease."
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