Association of Dopamine Beta-Hydroxylase Polymorphisms with Alzheimer’s Disease, Parkinson’s Disease and Schizophrenia: Evidence Based on Currently Available Loci

Tang, Siqi; Yao, Bin; Li, Na; Lin, Shuhuang; Huang, Zunnan

doi:10.1159/000495238

Cited by 20 publications

(11 citation statements)

References 59 publications

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“…DBH (dopamine β-hydroxylase) is a copper-containing oxygenase that catalyzes the conversion of dopamine to norepinephrine [60]. Not surprisingly, altered dopamine signalling has been linked to the NCLs, as well as other neurological disorders including Alzheimer's disease, Parkinson's disease, and schizophrenia [61][62][63][64][65]. Mutations in SLC25A1 are associated with impaired neuromuscular transmission [66].…”

Section: Protein Interactomes Shed Light On the Interactions Between mentioning

confidence: 99%

Molecular networking in the neuronal ceroid lipofuscinoses: insights from mammalian models and the social amoeba Dictyostelium discoideum

Huber

2020

J Biomed Sci

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The neuronal ceroid lipofuscinoses (NCLs), commonly known as Batten disease, belong to a family of neurological disorders that cause blindness, seizures, loss of motor function and cognitive ability, and premature death. There are 13 different subtypes of NCL that are associated with mutations in 13 genetically distinct genes (CLN1-CLN8, CLN10-CLN14). Similar clinical and pathological profiles of the different NCL subtypes suggest that common disease mechanisms may be involved. As a result, there have been many efforts to determine how NCL proteins are connected at the cellular level. A main driving force for NCL research has been the utilization of mammalian and non-mammalian cellular models to study the mechanisms underlying the disease. One non-mammalian model that has provided significant insight into NCL protein function is the social amoeba Dictyostelium discoideum. Accumulated data from Dictyostelium and mammalian cells show that NCL proteins display similar localizations, have common binding partners, and regulate the expression and activities of one another. In addition, genetic models of NCL display similar phenotypes. This review integrates findings from Dictyostelium and mammalian models of NCL to highlight our understanding of the molecular networking of NCL proteins. The goal here is to help set the stage for future work to reveal the cellular mechanisms underlying the NCLs.

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Section: Protein Interactomes Shed Light On the Interactions Between mentioning

confidence: 99%

Molecular networking in the neuronal ceroid lipofuscinoses: insights from mammalian models and the social amoeba Dictyostelium discoideum

Huber

2020

J Biomed Sci

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“…As alluded to earlier, altered protein and activity have been reported in both PD and AD. This can occur in several ways such as degeneration of LC noradrenergic neurons, neuroinflammation, and dysregulation of copper levels that are all associated with both neurological diseases (McMillan et al ; Trillo et al ; He et al ; Tang et al ; Peterson and Li ; Ross et al ).…”

Section: Dβh In Neurodegenerative Diseasementioning

confidence: 99%

Dopamine beta‐hydroxylase and its genetic variants in human health and disease

Gonzalez-Lopez

Vrana

2019

Journal of Neurochemistry

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Dopamine beta-hydroxylase (DbH) is an essential neurotransmitter-synthesizing enzyme that catalyzes the formation of norepinephrine (NE) from dopamine and has been extensively studied since its discovery in the 1950s. NE serves as a neurotransmitter in both the central and peripheral nervous systems and is the precursor to epinephrine synthesis in the brain and adrenal medulla. Alterations in noradrenergic signaling have been linked to both central nervous system and peripheral pathologies. DbH protein, which is found in circulation, can, therefore, be evaluated as a marker of norepinephrine function in a plethora of different disorders and diseases. In many of these diseases, DbH protein availability and activity are believed to contribute to disease presentation or select symptomology and are believed to be under strong genetic control. Alteration in the DbH protein by genetic polymorphisms may result in DbH becoming ratelimiting and directly contributing to lower NE and epinephrine levels and disease. With the completion of the human genome project and the advent of next-generation sequencing, new insights have been gained into the existence of naturally occurring DbH sequencing variants (genetic polymorphisms) in disease. Also, biophysical tools coupled with genetic sequences are illuminating structure-function relationships within the enzyme. In this review, we discuss the role of genetic variants in DbH and its role in health and disease.

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“…A wide variety of psychiatric and neurological disease processes are associated with these genes and brain regions. In particular, single nucleotide polymorphisms (SNPs) in ANKK1 and DRD2 have been associated with addictive behaviors [ 1 , 2 ] and schizophrenia [ 3 , 4 ], while variants in DBH , DRD1 , and DRD3 have been associated with Alzheimer’s Disease, Parkinson’s Disease, and cognitive performance in a number of different clinical populations [ 5 , 6 , 7 ]. Additionally, variants in DRD5 and SLC6A3 have been associated with attention deficit hyperactivity disorder (ADHD) [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Expression of Dopamine-Related Genes in Four Human Brain Regions

Stanfill

Cao

2020

Brain Sciences

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A better understanding of dopaminergic gene expression will inform future treatment options for many different neurologic and psychiatric conditions. Here, we utilized the National Institutes of Health’s Genotype-Tissue Expression project (GTEx) dataset to investigate genotype by expression associations in seven dopamine pathway genes (ANKK1, DBH, DRD1, DRD2, DRD3, DRD5, and SLC6A3) in and across four human brain tissues (prefrontal cortex, nucleus accumbens, substantia nigra, and hippocampus). We found that age alters expression of DRD1 in the nucleus accumbens and prefrontal cortex, DRD3 in the nucleus accumbens, and DRD5 in the hippocampus and prefrontal cortex. Sex was associated with expression of DRD5 in substantia nigra and hippocampus, and SLC6A3 in substantia nigra. We found that three linkage disequilibrium blocks of SNPs, all located in DRD2, were associated with alterations in expression across all four tissues. These demographic characteristic associations and these variants should be further investigated for use in screening, diagnosis, and future treatment of neurological and psychiatric conditions.

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Association of Dopamine Beta-Hydroxylase Polymorphisms with Alzheimer’s Disease, Parkinson’s Disease and Schizophrenia: Evidence Based on Currently Available Loci

Cited by 20 publications

References 59 publications

Molecular networking in the neuronal ceroid lipofuscinoses: insights from mammalian models and the social amoeba Dictyostelium discoideum

Molecular networking in the neuronal ceroid lipofuscinoses: insights from mammalian models and the social amoeba Dictyostelium discoideum

Dopamine beta‐hydroxylase and its genetic variants in human health and disease

Expression of Dopamine-Related Genes in Four Human Brain Regions

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