Glyceraldehyde-3-phosphate Dehydrogenase is a Multifaceted Therapeutic Target

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2020 May 7

PMID 32370188

Citations 32

Authors

Vladimir F Lazarev

Irina V Guzhova

Boris A Margulis

Affiliations

Soon will be listed here.

Abstract

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a glycolytic enzyme whose role in cell metabolism and homeostasis is well defined, while its function in pathologic processes needs further elucidation. Depending on the cell context, GAPDH may bind a number of physiologically important proteins, control their function and correspondingly affect the cell's fate. These interprotein interactions and post-translational modifications of GAPDH mediate its cytotoxic or cytoprotective functions in the manner of a Janus-like molecule. In this review, we discuss the functional features of the enzyme in cellular physiology and its possible involvement in human pathologies. In the last part of the article, we describe drugs that can be employed to modulate this enzyme's function in some pathologic states.

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References

Hwang S, Disatnik M, Mochly-Rosen D . Impaired GAPDH-induced mitophagy contributes to the pathology of Huntington's disease. EMBO Mol Med. 2015; 7(10):1307-26. PMC: 4604685. DOI: 10.15252/emmm.201505256. View

Suarez S, McCollum G, Jayagopal A, Penn J . High Glucose-induced Retinal Pericyte Apoptosis Depends on Association of GAPDH and Siah1. J Biol Chem. 2015; 290(47):28311-28320. PMC: 4653686. DOI: 10.1074/jbc.M115.682385. View

Warburg O, Wind F, Negelein E . THE METABOLISM OF TUMORS IN THE BODY. J Gen Physiol. 2009; 8(6):519-30. PMC: 2140820. DOI: 10.1085/jgp.8.6.519. View

Tisdale E, Talati N, Artalejo C, Shisheva A . GAPDH binds Akt to facilitate cargo transport in the early secretory pathway. Exp Cell Res. 2016; 349(2):310-319. PMC: 5129630. DOI: 10.1016/j.yexcr.2016.10.025. View

Naletova I, Schmalhausen E, Kharitonov A, Katrukha A, Saso L, Caprioli A . Non-native glyceraldehyde-3-phosphate dehydrogenase can be an intrinsic component of amyloid structures. Biochim Biophys Acta. 2008; 1784(12):2052-8. DOI: 10.1016/j.bbapap.2008.07.013. View

Fugier E, Salcedo S, de Chastellier C, Pophillat M, Muller A, Arce-Gorvel V . The glyceraldehyde-3-phosphate dehydrogenase and the small GTPase Rab 2 are crucial for Brucella replication. PLoS Pathog. 2009; 5(6):e1000487. PMC: 2695806. DOI: 10.1371/journal.ppat.1000487. View

Guzhova I, Lazarev V, Kaznacheeva A, Ippolitova M, Muronetz V, Kinev A . Novel mechanism of Hsp70 chaperone-mediated prevention of polyglutamine aggregates in a cellular model of huntington disease. Hum Mol Genet. 2011; 20(20):3953-63. DOI: 10.1093/hmg/ddr314. View

Landino L, Hagedorn T, Kennett K . Evidence for thiol/disulfide exchange reactions between tubulin and glyceraldehyde-3-phosphate dehydrogenase. Cytoskeleton (Hoboken). 2014; 71(12):707-18. DOI: 10.1002/cm.21204. View

Muronetz V, Barinova K, Stroylova Y, Semenyuk P, Schmalhausen E . Glyceraldehyde-3-phosphate dehydrogenase: Aggregation mechanisms and impact on amyloid neurodegenerative diseases. Int J Biol Macromol. 2016; 100:55-66. DOI: 10.1016/j.ijbiomac.2016.05.066. View

10.

Liu J, Wang Y, Gong L, Sun C . Oxidation of glyceraldehyde-3-phosphate dehydrogenase decreases sperm motility in diabetes mellitus. Biochem Biophys Res Commun. 2015; 465(2):245-8. DOI: 10.1016/j.bbrc.2015.08.006. View

11.

Lazarev V, Dutysheva E, Komarova E, Guzhova I, Margulis B . Hydrocortisone 21-hemisuccinate did not prevent exogenous GAPDH-induced apoptosis in human neuroblastoma cells. Data Brief. 2018; 20:899-902. PMC: 6138975. DOI: 10.1016/j.dib.2018.08.093. View

12.

Carrillo M, Kanai S, Kitani K, Ivy G . A high dose of long term treatment with deprenyl loses its effect on antioxidant enzyme activities as well as on survivals of Fischer-344 rats. Life Sci. 2000; 67(21):2539-48. DOI: 10.1016/s0024-3205(00)00838-9. View

13.

Barinova K, Khomyakova E, Semenyuk P, Schmalhausen E, Muronetz V . Binding of alpha-synuclein to partially oxidized glyceraldehyde-3-phosphate dehydrogenase induces subsequent inactivation of the enzyme. Arch Biochem Biophys. 2018; 642:10-22. DOI: 10.1016/j.abb.2018.02.002. View

14.

Zhang J, Qiao N, Ding X, Wang J . Disruption of the GluA2/GAPDH complex using TAT-GluA2NT1-3-2 peptide protects against AMPAR-mediated excitotoxicity after epilepsy. Neuroreport. 2018; 29(5):432-439. DOI: 10.1097/WNR.0000000000000996. View

15.

Verdier Y, Foldi I, Sergeant N, Fulop L, Penke Z, Janaky T . Characterization of the interaction between Abeta 1-42 and glyceraldehyde phosphodehydrogenase. J Pept Sci. 2008; 14(6):755-62. DOI: 10.1002/psc.998. View

16.

Chen Y, He R, Liu Y, Xue Z . Effect of human neuronal tau on denaturation and reactivation of rabbit muscle D-glyceraldehyde-3-phosphate dehydrogenase. Biochem J. 2000; 351(Pt 1):233-40. PMC: 1221354. DOI: 10.1042/0264-6021:3510233. View

17.

Nakajima H, Amano W, Fujita A, Fukuhara A, Azuma Y, Hata F . The active site cysteine of the proapoptotic protein glyceraldehyde-3-phosphate dehydrogenase is essential in oxidative stress-induced aggregation and cell death. J Biol Chem. 2007; 282(36):26562-74. DOI: 10.1074/jbc.M704199200. View

18.

Millet P, Vachharajani V, McPhail L, Yoza B, McCall C . GAPDH Binding to TNF-α mRNA Contributes to Posttranscriptional Repression in Monocytes: A Novel Mechanism of Communication between Inflammation and Metabolism. J Immunol. 2016; 196(6):2541-51. PMC: 4779706. DOI: 10.4049/jimmunol.1501345. View

19.

Li T, Tan X, Yang R, Miao Y, Zhang M, Xi Y . Discovery of novel glyceraldehyde-3-phosphate dehydrogenase inhibitor via docking-based virtual screening. Bioorg Chem. 2020; 96:103620. DOI: 10.1016/j.bioorg.2020.103620. View

20.

Xing C, LaPorte J, Barbay J, Myers A . Identification of GAPDH as a protein target of the saframycin antiproliferative agents. Proc Natl Acad Sci U S A. 2004; 101(16):5862-6. PMC: 395888. DOI: 10.1073/pnas.0307476101. View