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Atremorine in Parkinson's disease: From dopaminergic neuroprotection to pharmacogenomics
Author(s) -
Cacabelos Ramón,
Carrera Iván,
Martínez Olaia,
Alejo Ramón,
FernándezNovoa Lucía,
Cacabelos Pablo,
Corzo Lola,
Rodríguez Susana,
Alcaraz Margarita,
Nebril Laura,
Tellado Iván,
Cacabelos Natalia,
Pego Rocío,
Naidoo Vinogran,
Carril Juan C.
Publication year - 2021
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.21838
Subject(s) - neuroprotection , dopaminergic , pharmacology , dopamine , dopamine transporter , parkinson's disease , medicine , pharmacogenomics , endocrinology , disease
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.