Epigenetics is the study of how cells control gene activity without changing the DNA sequence. Epigenetic changes affect how genes are turned on and off or expressed, and thus help regulate how cells in different parts of the body use the same genetic code. Errors in the epigenetic process can not only lead to abnormal gene activity or inactivity, but can also influence alternative splicing (AS) and could cause human diseases. Understanding of how epigenetic defects can affect human health, especially for neurological disorders, could suggest targets for therapeutic interventions. For such a purpose, the Lesch-Nyhan disease (LND) has been selected as a valuable model to study the genetic-epigenetic interplay, especially to explore the epistasis between the housekeeping hypoxanthine phosphoribosyltransferase 1 (HPRT1) and β-amyloid precursor protein (APP) genes. This review is structured as follows: we begin with an overview about the monogenetic neurological disorders associated with epigenetic changes; next, the current knowledge on HPRT1 and APP genes is provided; then, the epistasis between HPRT1 and APP genes related to the neurobehavioral syndrome in LND is described; and finally, we present the construction of expression vectors to study intermolecular interactions between the hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme and APP in LND. Information obtained from such expression vectors would be useful for future directions to design therapies through epigenetic interventions.
Citation: Khue Vu Nguyen. Epigenetic modulation of human neurobiological disorders: Lesch-Nyhan disease as a model disorder[J]. AIMS Neuroscience, 2025, 12(2): 58-74. doi: 10.3934/Neuroscience.2025005
Epigenetics is the study of how cells control gene activity without changing the DNA sequence. Epigenetic changes affect how genes are turned on and off or expressed, and thus help regulate how cells in different parts of the body use the same genetic code. Errors in the epigenetic process can not only lead to abnormal gene activity or inactivity, but can also influence alternative splicing (AS) and could cause human diseases. Understanding of how epigenetic defects can affect human health, especially for neurological disorders, could suggest targets for therapeutic interventions. For such a purpose, the Lesch-Nyhan disease (LND) has been selected as a valuable model to study the genetic-epigenetic interplay, especially to explore the epistasis between the housekeeping hypoxanthine phosphoribosyltransferase 1 (HPRT1) and β-amyloid precursor protein (APP) genes. This review is structured as follows: we begin with an overview about the monogenetic neurological disorders associated with epigenetic changes; next, the current knowledge on HPRT1 and APP genes is provided; then, the epistasis between HPRT1 and APP genes related to the neurobehavioral syndrome in LND is described; and finally, we present the construction of expression vectors to study intermolecular interactions between the hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme and APP in LND. Information obtained from such expression vectors would be useful for future directions to design therapies through epigenetic interventions.
Angiotensin-converting enzyme 2
acetyl coenzyme A
Alzheimer's disease
A disintegrin and metalloprotease-10
APP intracellular domain
Amyotrophic lateral sclerosis
β-amyloid precursor protein
APP-like protein-2
Soluble APP derivative obtained after cleavage by α-secretase
Soluble APP derivative obtained after cleavage by β-secretase
APP-α-carboxyl-terminal fragment
APP-β-carboxyl-terminal fragment
Alternative splicing
Amyloid-β peptide
Alanine at position 713
cytidine analogues 5-azacytidine
β-site APP cleaving enzyme 1
Bromodomain and extraterminal
Carbonic anhydrase
entire coding sequence
Coronavirus disease 2019 virus
Central nervous system
Deoxyribonucleic acid
DNA methyltransferases
Extracellular domain
Euchromatic histone-lysine N-methyltransferase 1
Familial AD
human folate receptor 1
Fragile X syndrome
Green fluorescent protein
G9a-like protein
Guanosine monophosphate
Glycosylphosphatidylinositol
GPI-anchored proteins
Histone acetyltransferases
Histone deacetylases
Hypoxanthine-guanine phosphoribosyltransferase
Human leukocyte antigen
Hypoxanthine phosphoribosyltransferase 1
Histone methyltransferases
Intracellular domain
Inosine monophosphate
Deletion followed by an insertion
Kunitz-type serine protease inhibitor
Lysine at position 687
Lesch-Nyhan disease
Lessh-Nyhan variants
Methyl-CpG-binding
Methyl CpG binding protein 2
Mendelian inheritance in man
Messenger RNA
Multiple sclerosis
Methionine at position 671
Neurofibrillary tangles
National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's disease and Related Disorder Association
phosphogluconate dehydrogenase
Precursor mRNA
Cellular prion protein (the ubiquitous normal cellular form)
α-D-5-phosphoribosyl-1-pyrophosphate
Presenilin
Ribonucleic acid
Sporadic AD
Severe acute respiratory syndrome coronavirus 2
Spike glycoprotein
Single-nucleotide polymorphism
Senile plaques
Transmembrane domain
Transmissible spongiform encephalopathies
Valine at position 711
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Figures(3)
Khue Vu Nguyen. Epigenetic modulation of human neurobiological disorders: Lesch-Nyhan disease as a model disorder[J]. AIMS Neuroscience, 2025, 12(2): 58-74. doi: 10.3934/Neuroscience.2025005
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