Atremorine in Parkinson's disease: From dopaminergic neuroprotection to pharmacogenomics
| Autor: | Olaia Martínez, Rocío Pego, Juan C. Carril, Laura Nebril, Ramón Cacabelos, Pablo Cacabelos, Iván Carrera, Natalia Cacabelos, Lucía Fernández-Novoa, Iván Tellado, Lola Corzo, Susana Rodríguez, Vinogran Naidoo, Ramón Alejo, Margarita Alcaraz |
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| Rok vydání: | 2021 |
| Předmět: |
Apolipoprotein E
Parkinson's disease Arylamine N-Acetyltransferase Dopamine Pharmacology Neuroprotection Levodopa 03 medical and health sciences 0302 clinical medicine Drug Discovery medicine Humans 030304 developmental biology Serotonin Plasma Membrane Transport Proteins 0303 health sciences Dopamine Plasma Membrane Transport Proteins Membrane Glycoproteins business.industry Dopaminergic Parkinson Disease medicine.disease LRRK2 Prolactin Pharmacogenetics 030220 oncology & carcinogenesis Molecular Medicine Serotonin business medicine.drug |
| Zdroj: | Medicinal research reviewsREFERENCES. 41(5) |
| ISSN: | 1098-1128 |
| Popis: | Atremorine is a novel bioproduct obtained by nondenaturing biotechnological processes from a genetic species of Vicia faba. Atremorine is a potent dopamine (DA) enhancer with powerful effects on the neuronal dopaminergic system, acting as a neuroprotective agent in Parkinson's disease (PD). Over 97% of PD patients respond to a single dose of Atremorine (5 g, p.o.) 1 h after administration. This response is gender-, time-, dose-, and genotype-dependent, with optimal doses ranging from 5 to 20 g/day, depending upon disease severity and concomitant medication. Drug-free patients show an increase in DA levels from 12.14 ± 0.34 pg/ml to 6463.21 ± 1306.90 pg/ml; and patients chronically treated with anti-PD drugs show an increase in DA levels from 1321.53 ± 389.94 pg/ml to 16,028.54 ± 4783.98 pg/ml, indicating that Atremorine potentiates the dopaminergic effects of conventional anti-PD drugs. Atremorine also influences the levels of other neurotransmitters (adrenaline, noradrenaline) and hormones which are regulated by DA (e.g., prolactin, PRL), with no effect on serotonin or histamine. The variability in Atremorine-induced DA response is highly attributable to pharmacogenetic factors. Polymorphic variants in pathogenic (SNCA, NUCKS1, ITGA8, GPNMB, GCH1, BCKDK, APOE, LRRK2, ACMSD), mechanistic (DRD2), metabolic (CYP2D6, CYP2C9, CYP2C19, CYP3A4/5, NAT2), transporter (ABCB1, SLC6A2, SLC6A3, SLC6A4) and pleiotropic genes (APOE) influence the DA response to Atremorine and its psychomotor and brain effects. Atremorine enhances DNA methylation and displays epigenetic activity via modulation of the pharmacoepigenetic network. Atremorine is a novel neuroprotective agent for dopaminergic neurons with potential prophylactic and therapeutic activity in PD. |
| Databáze: | OpenAIRE |
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