title: A review of the implication of hypoxanthine excess in the physiopathology of Lesch-Nyhan disease.
abstract: Lesch-Nyhan disease is caused by HGprt deficiency, however, the mechanism by which enzyme deficiency leads to the severe neurological manifestations is still unknown. We hypothesized that hypoxanthine excess leads, directly or indirectly, through its action in adenosine transport, to aberrations in neuronal development. We found that hypoxanthine diminishes adenosine transport and enhances stimulation of adenosine receptors. These effects cause an imbalance between adenosine, dopamine, and serotonin receptors in HGprt deficient cells, and cells differentiated with hypoxanthine showed an increase in dopamine, adenosine and serotonin receptors expression. Hypoxanthine deregulates early neuronal differentiation increasing WNT4 and EN1 gene expression.
authors.affiliation: a Department of Biochemistry , La Paz University Hospital, IdiPaz, Madrid, Spain and Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII , Spain.
authors.forename: R J
authors.initials: RJ
authors.lastname: Torres
authors.affiliation: a Department of Biochemistry , La Paz University Hospital, IdiPaz, Madrid, Spain and Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII , Spain.
authors.forename: C
authors.initials: C
authors.lastname: Prior
authors.affiliation: a Department of Biochemistry , La Paz University Hospital, IdiPaz, Madrid, Spain and Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII , Spain.
authors.forename: M G
authors.initials: MG
authors.lastname: Garcia
authors.affiliation: b Department of Internal Medicine , Metabolic-Vascular Unit, La Paz University Hospital , IdiPaz , Madrid , Spain.
authors.forename: J G
authors.initials: JG
authors.lastname: Puig
mesh_terms: D000241:Adenosine / Q000378:metabolism; D001692:Biological Transport; D002454:Cell Differentiation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019271:Hypoxanthine / Q000502:physiology*; D007926:Lesch-Nyhan Syndrome / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D009474:Neurons / Q000502:physiology; D060528:Wnt4 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C513076:EN1 protein, human; D018398:Homeodomain Proteins; C555581:WNT4 protein, human; D060528:Wnt4 Protein; D019271:Hypoxanthine; D000241:Adenosine
keywords: HPRT; Lesch–Nyhan; NTERA-2; hypoxanthine