ArticleNeurobiology of disease2010
Hsp70- and Hsp90-mediated proteasomal degradation underlies TPI sugarkill pathogenesis in Drosophila.
Article in Neurobiology of disease, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- Article
- Discovery and validation of small molecule stabilizers of mutant triose phosphate isomerase (TPI) as potential lead candidates for TPI deficiency.SLAS discovery : advancing life sciences R & D · 2025Article
- Itavastatin and resveratrol increase triosephosphate isomerase protein in a newly identified variant of TPI deficiency.Disease models & mechanisms · 2022Article
- Murine model of triosephosphate isomerase deficiency with anemia and severe neuromuscular dysfunction.Current research in neurobiology · 2022Article
- A High-Content Screening Assay for Small Molecules That Stabilize Mutant Triose Phosphate Isomerase (TPI) as Treatments for TPI Deficiency.SLAS discovery : advancing life sciences R & D · 2021Article
- Identification of protein quality control regulators using a Drosophila model of TPI deficiency.Neurobiology of disease · 2021Article
- Missense variant in TPI1 (Arg189Gln) causes neurologic deficits through structural changes in the triosephosphate isomerase catalytic site and reduced enzyme levels in vivo.Biochimica et biophysica acta. Molecular basis of disease · 2019Article
- Bone marrow transplantation corrects haemolytic anaemia in a novel ENU mutagenesis mouse model of TPI deficiency.Disease models & mechanisms · 2018Article
- Hsp83 loss suppresses proteasomal activity resulting in an upregulation of caspase-dependent compensatory autophagy.Autophagy · 2017Article
- Structural and Genetic Studies Demonstrate Neurologic Dysfunction in Triosephosphate Isomerase Deficiency Is Associated with Impaired Synaptic Vesicle Dynamics.PLoS genetics · 2016Article
- Triosephosphate isomerase I170V alters catalytic site, enhances stability and induces pathology in a Drosophila model of TPI deficiency.Biochimica et biophysica acta · 2015Article
- Evidence of a triosephosphate isomerase non-catalytic function crucial to behavior and longevity.Journal of cell science · 2013Article
- Early mitochondrial dysfunction leads to altered redox chemistry underlying pathogenesis of TPI deficiency.Neurobiology of disease · 2013Article
- Nicotinamide mononucleotide adenylyltransferase maintains active zone structure by stabilizing Bruchpilot.EMBO reports · 2013Article
- A novel Drosophila SOD2 mutant demonstrates a role for mitochondrial ROS in neurodevelopment and disease.Brain and behavior · 2012Article
- Genetically encoded redox sensor identifies the role of ROS in degenerative and mitochondrial disease pathogenesis.Neurobiology of disease · 2012Article
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2 authors at 1 institution in 1 country.
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Abstract
Triosephosphate isomerase (TPI) deficiency is a severe glycolytic enzymopathy that causes progressive locomotor impairment and neurodegeneration, susceptibility to infection, and premature death. The recessive missense TPI(sugarkill) mutation in Drosophila melanogaster exhibits phenotypes analogous to human TPI deficiency such as progressive locomotor impairment, neurodegeneration, and reduced life span. We have shown that the TPI(sugarkill) protein is an active stable dimer; however, the mutant protein is turned over by the proteasome reducing cellular levels of this glycolytic enzyme. As proteasome function is often coupled with molecular chaperone activity, we hypothesized that TPI(sugarkill) is recognized by molecular chaperones that mediate the proteasomal degradation of the mutant protein. Coimmunoprecipitation data and analyses of TPI(sugarkill) turnover in animals with reduced or enhanced molecular chaperone activity indicate that both Hsp90 and Hsp70 are important for targeting TPI(sugarkill) for degradation. Furthermore, molecular chaperone and proteasome activity modified by pharmacological or genetic manipulations resulted in improved TPI(sugarkill) protein levels and rescue some but not all of the disease phenotypes suggesting that TPI deficiency pathology is complex. Overall, these data demonstrate a surprising role for Hsp70 and Hsp90 in the progression of neural dysfunction associated with TPI deficiency.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.