Murine model of triosephosphate isomerase deficiency with anemia and severe neuromuscular dysfunction

Myers, Tracey; Ferguson, Carolyn; Gliniak, Eric; Homanics, Gregg E.; Palladino, Michael J.

doi:10.1016/j.crneur.2022.100062

Cited by 2 publications

(1 citation statement)

References 25 publications

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“…Consistent with these findings it is known that TPI Df causing mutations, such as TPI1 E105D , affect the stability of TPI resulting in severe phenotypes (Schneider et al 1965 ; Vives-Corrons et al 1978 ). When modeling the TPI1 E105D mutation within the mouse, the phenotype was found to strongly resemble the human disease symptomology and this phenotype was accompanied by a strong decrease in the amount of TPI protein (Myers et al 2022 ). These data support the conclusion that it is loss of stability and lowered TPI levels ( affecting all TPI functions ) that underlie the disease and open up the possibility that loss of non-glycolytic functions of TPI may contribute to the disease, especially within the neuromuscular system.…”

Section: Evidence For a Potential Non-catalytic Tpi Functionmentioning

confidence: 99%

Newly discovered roles of triosephosphate isomerase including functions within the nucleus

Myers

Palladino

2023

Mol Med

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Triosephosphate isomerase (TPI) is best known as a glycolytic enzyme that interconverts the 3-carbon sugars dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P). TPI is an essential enzyme that is required for the catabolism of DHAP and a net yield of ATP from anaerobic glucose metabolism. Loss of TPI function results in the recessive disease TPI Deficiency (TPI Df). Recently, numerous lines of evidence suggest the TPI protein has other functions beyond glycolysis, a phenomenon known as moonlighting or gene sharing. Here we review the numerous functions ascribed to TPI, including recent findings of a nuclear role of TPI implicated in cancer pathogenesis and chemotherapy resistance.

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Section: Evidence For a Potential Non-catalytic Tpi Functionmentioning

confidence: 99%

Newly discovered roles of triosephosphate isomerase including functions within the nucleus

Myers

Palladino

2023

Mol Med

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Neuromuscular dysfunction and pathogenesis in triosephosphate isomerase deficiency

Myers,

Li,

Taiclet

et al. 2024

Sci Rep

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Triosephosphate isomerase deficiency (TPI Df) is a rare multisystem disorder with severe neuromuscular symptoms which arises exclusively from mutations within the TPI1 gene. Studies of TPI Df have been limited due to the absence of mammalian disease models and difficulties obtaining patient samples. Recently, we developed a novel murine model of TPI Df which models the most common disease-causing mutation in humans, TPI1 E105D . Using our model in the present study, the underlying pathogenesis of neuromuscular symptoms has been elucidated. This is the first report detailing studies of neuromuscular pathology within a murine model of TPI Df. We identified several contributors to neuromuscular symptoms, including neurodegeneration in the brain, alterations in neurotransmission at the neuromuscular junction, and reduced muscle fiber size. TPI Df mice also exhibited signs of cardiac pathology and displayed a deficit in vascular smooth muscle functionality. Together, these findings provide insight into pathogenesis of the neuromuscular symptoms in TPI Df and can guide the future development of therapeutics.

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Murine model of triosephosphate isomerase deficiency with anemia and severe neuromuscular dysfunction

Cited by 2 publications

References 25 publications

Newly discovered roles of triosephosphate isomerase including functions within the nucleus

Newly discovered roles of triosephosphate isomerase including functions within the nucleus

Neuromuscular dysfunction and pathogenesis in triosephosphate isomerase deficiency

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