{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T03:16:27Z","timestamp":1778814987020,"version":"3.51.4"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2008,6,1]],"date-time":"2008-06-01T00:00:00Z","timestamp":1212278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Triose phosphate isomerase (TPI) deficiency glycolytic enzymopathy is a progressive neurodegenerative condition that remains poorly understood. The disease is caused exclusively by specific missense mutations affecting the TPI protein and clinically features hemolytic anemia, adult-onset neurological impairment, degeneration, and reduced longevity. TPI has a well-characterized role in glycolysis, catalyzing the isomerization of dihydroxyacetone phosphate (DHAP) to glyceraldehyde-3-phosphate (G3P); however, little is known mechanistically about the pathogenesis associated with specific recessive mutations that cause progressive neurodegeneration. Here, we describe key aspects of TPI pathogenesis identified using the TPIsugarkill mutation, a Drosophila model of human TPI deficiency. Specifically, we demonstrate that the mutant protein is expressed, capable of forming a homodimer, and is functional. However, the mutant protein is degraded by the 20S proteasome core leading to loss-of-function pathogenesis.<\/jats:p>","DOI":"10.1534\/genetics.108.087551","type":"journal-article","created":{"date-parts":[[2008,5,6]],"date-time":"2008-05-06T00:34:12Z","timestamp":1210034052000},"page":"855-862","source":"Crossref","is-referenced-by-count":30,"title":["Degradation of Functional Triose Phosphate Isomerase Protein Underlies<i>sugarkill<\/i>Pathology"],"prefix":"10.1093","volume":"179","author":[{"given":"Jacquelyn L","family":"Seigle","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicia M","family":"Celotto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J","family":"Palladino","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology , University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261 and Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,6,1]]},"reference":[{"key":"2022110410385427800_BIB1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.bbadis.2003.08.002","volume":"1639","year":"2003","journal-title":"Biochim. 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