Potential molecular link between the β-amyloid precursor protein (APP) and hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme in Lesch-Nyhan disease and cancer

Lesch-Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorders of purine metabolic in which the cytoplasmic enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. Despite having been characterized over 60 years ago, however, up to now, there is no satisfactory ex...

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Autor principal:	Khue Vu Nguyen
Formato:	article
Lenguaje:	EN
Publicado:	AIMS Press 2021
Materias:	β-amyloid precursor protein (app) hypoxanthine-guanine phosphoribosyltransferase (hgprt) enzyme app gene hypoxanthine phosphoribosyltransferase 1 (hprt1) gene epistasis epigenetics alternative splicing lesch-nyhan disease covid-19 thrombosis cancer antisense drugs Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/87a45eae98444dcf8a8626b01e50e7e2
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spelling	oai:doaj.org-article:87a45eae98444dcf8a8626b01e50e7e22021-12-02T01:23:48ZPotential molecular link between the β-amyloid precursor protein (APP) and hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme in Lesch-Nyhan disease and cancer10.3934/Neuroscience.20210302373-7972https://doaj.org/article/87a45eae98444dcf8a8626b01e50e7e22021-10-01T00:00:00Zhttps://www.aimspress.com/article/doi/10.3934/Neuroscience.2021030?viewType=HTMLhttps://doaj.org/toc/2373-7972Lesch-Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorders of purine metabolic in which the cytoplasmic enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. Despite having been characterized over 60 years ago, however, up to now, there is no satisfactory explanation of how deficits in enzyme HGprt can lead to LND with the development of the persistent and severe self-injurious behavior. Recently, a role for epistasis between the mutated hypoxanthine phosphoribosyltransferase 1 (HPRT1) and the β-amyloid precursor protein (APP) genes affecting the regulation of alternative APP pre-mRNA splicing in LND has been demonstrated. Furthermore, there were also some reported cases of LND developing thrombosis while APP is an important regulator of vein thrombosis and controls coagulation. Otherwise, the surface expression of HGprt enzyme was also observed in several somatic tissue cancers while APP and the APP-like protein-2 (APLP2) are deregulated in cancer cells and linked to increased tumor cell proliferation, migration, and invasion. The present review provides a discussion about these findings and suggests a potential molecular link between APP and HGprt via epistasis between HPRT1 and APP genes affecting the regulation of alternative APP pre-mRNA splicing. As a perspective, expression vectors for HGprt enzyme and APP are constructed as described in Ref. # 24 (Nguyen KV, Naviaux RK, Nyhan WL (2020) Lesch-Nyhan disease: I. Construction of expression vectors for hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme and amyloid precursor protein (APP). Nucleosides Nucleotides Nucleic Acids 39: 905–922), and they could be used as tools for clarification of these issues. In addition, these expression vectors, especially the one with the glycosyl-phosphatidylinositol (GPI) anchor can be used as a model for the construction of expression vectors for any protein targeting to the cell plasma membrane for studying intermolecular interactions and could be therefore useful in the vaccines as well as antiviral drugs development (studying intermolecular interactions between the spike glycoprotein of the severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, as well as its variants and the angiotensin-converting enzyme 2, ACE2, in coronavirus disease 2019 (COVID-19) [43],[44], for example).Khue Vu NguyenAIMS Pressarticleβ-amyloid precursor protein (app)hypoxanthine-guanine phosphoribosyltransferase (hgprt) enzymeapp genehypoxanthine phosphoribosyltransferase 1 (hprt1) geneepistasisepigeneticsalternative splicinglesch-nyhan diseasecovid-19thrombosiscancerantisense drugsNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENAIMS Neuroscience, Vol 8, Iss 4, Pp 548-557 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	β-amyloid precursor protein (app) hypoxanthine-guanine phosphoribosyltransferase (hgprt) enzyme app gene hypoxanthine phosphoribosyltransferase 1 (hprt1) gene epistasis epigenetics alternative splicing lesch-nyhan disease covid-19 thrombosis cancer antisense drugs Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	β-amyloid precursor protein (app) hypoxanthine-guanine phosphoribosyltransferase (hgprt) enzyme app gene hypoxanthine phosphoribosyltransferase 1 (hprt1) gene epistasis epigenetics alternative splicing lesch-nyhan disease covid-19 thrombosis cancer antisense drugs Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Khue Vu Nguyen Potential molecular link between the β-amyloid precursor protein (APP) and hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme in Lesch-Nyhan disease and cancer
description	Lesch-Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorders of purine metabolic in which the cytoplasmic enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. Despite having been characterized over 60 years ago, however, up to now, there is no satisfactory explanation of how deficits in enzyme HGprt can lead to LND with the development of the persistent and severe self-injurious behavior. Recently, a role for epistasis between the mutated hypoxanthine phosphoribosyltransferase 1 (HPRT1) and the β-amyloid precursor protein (APP) genes affecting the regulation of alternative APP pre-mRNA splicing in LND has been demonstrated. Furthermore, there were also some reported cases of LND developing thrombosis while APP is an important regulator of vein thrombosis and controls coagulation. Otherwise, the surface expression of HGprt enzyme was also observed in several somatic tissue cancers while APP and the APP-like protein-2 (APLP2) are deregulated in cancer cells and linked to increased tumor cell proliferation, migration, and invasion. The present review provides a discussion about these findings and suggests a potential molecular link between APP and HGprt via epistasis between HPRT1 and APP genes affecting the regulation of alternative APP pre-mRNA splicing. As a perspective, expression vectors for HGprt enzyme and APP are constructed as described in Ref. # 24 (Nguyen KV, Naviaux RK, Nyhan WL (2020) Lesch-Nyhan disease: I. Construction of expression vectors for hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme and amyloid precursor protein (APP). Nucleosides Nucleotides Nucleic Acids 39: 905–922), and they could be used as tools for clarification of these issues. In addition, these expression vectors, especially the one with the glycosyl-phosphatidylinositol (GPI) anchor can be used as a model for the construction of expression vectors for any protein targeting to the cell plasma membrane for studying intermolecular interactions and could be therefore useful in the vaccines as well as antiviral drugs development (studying intermolecular interactions between the spike glycoprotein of the severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, as well as its variants and the angiotensin-converting enzyme 2, ACE2, in coronavirus disease 2019 (COVID-19) [43],[44], for example).
format	article
author	Khue Vu Nguyen
author_facet	Khue Vu Nguyen
author_sort	Khue Vu Nguyen
title	Potential molecular link between the β-amyloid precursor protein (APP) and hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme in Lesch-Nyhan disease and cancer
title_short	Potential molecular link between the β-amyloid precursor protein (APP) and hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme in Lesch-Nyhan disease and cancer
title_full	Potential molecular link between the β-amyloid precursor protein (APP) and hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme in Lesch-Nyhan disease and cancer
title_fullStr	Potential molecular link between the β-amyloid precursor protein (APP) and hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme in Lesch-Nyhan disease and cancer
title_full_unstemmed	Potential molecular link between the β-amyloid precursor protein (APP) and hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme in Lesch-Nyhan disease and cancer
title_sort	potential molecular link between the β-amyloid precursor protein (app) and hypoxanthine-guanine phosphoribosyltransferase (hgprt) enzyme in lesch-nyhan disease and cancer
publisher	AIMS Press
publishDate	2021
url	https://doaj.org/article/87a45eae98444dcf8a8626b01e50e7e2
work_keys_str_mv	AT khuevunguyen potentialmolecularlinkbetweenthebamyloidprecursorproteinappandhypoxanthineguaninephosphoribosyltransferasehgprtenzymeinleschnyhandiseaseandcancer
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Potential molecular link between the β-amyloid precursor protein (APP) and hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme in Lesch-Nyhan disease and cancer

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