Atremorine in Parkinson's disease: From dopaminergic neuroprotection to pharmacogenomics.

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.

Nutrition, Health, and Disease: Role of Selected Marine and Vegetal Nutraceuticals.

The investigation of new alternatives for disease prevention through the application of findings from dietary and food biotechnology is an ongoing challenge for the scientific community. New nutritional trends and the need to meet social and health demands have inspired the concept of functional foods and nutraceuticals which, in addition to their overall nutritional value, present certain properties for the maintenance of health. However, these effects are not universal. Nutrigenetics describes how the genetic profile has an impact on the response of the body to bioactive food components by influencing their absorption, metabolism, and site of action. The EbioSea Program, for biomarine prospection, and the Blue Butterfly Program, for the screening of vegetable-derived bioproducts, have identified a new series of nutraceuticals, devoid of side effects at conventional doses, with genotype-dependent preventive and therapeutic activity. Nutrigenomics and nutrigenetics provide the opportunity to explore the inter-individual differences in the metabolism of and response to nutrients, achieving optimal results. This fact leads to the concept of personalized nutrition as opposed to public health nutrition. Consequently, the development and prescription of nutraceuticals according to the individual genetic profile is essential to improve their effectiveness in the prevention and natural treatment of prevalent diseases.

Pharmacogenetics of Atremorine-Induced Neuroprotection and Dopamine Response in Parkinson's Disease.

Atremorine is a novel bioproduct with neuroprotective effects on dopaminergic neurons and a natural L-DOPA donor in Parkinson's disease (PD). In the present study, we show the effects of a single dose of Atremorine (5 g, p. o.) on plasma dopamine (DA) response and brain function in PD (n = 183) and the influence that pathogenic (LRRK2), metabolic (CYP2D5, CYP2C9, CYP2C19, CYP3A5, NAT2), transporter (ABCB1), pleiotropic (APOE), and detoxifying genes (CYP1B1, GSTT1, GSTP1, GSTM1, SOD2) involved in the pharmacogenetic network exerts on Atremorine-induced DA response. Over 90% of PD patients at diagnosis show plasma DA levels below 20 pg/mL. Atremorine induces DA synthesis causing a significant increase in plasma DA levels 1 h after administration in practically 100% of patients. Females tend to show lower basal DA levels than males and the response of DA to Atremorine is stronger in males than in females. Atremorine-induced DA response is pharmacogenotype-specific and lasts from 6 - 12 h depending upon the pharmacogenetic profile of each patient. Genetic variants in pathogenic genes, metabolic genes, and genes involved in the detoxification processes affect the response of DA to Atremorine in a genotype-specific manner. Atremorine or any of its bioactive components can cross the blood-brain barrier and improve brain function and motor function, as revealed by the reduction in slow wave activity in brain mapping and psychometric assessment, respectively. Atremorine is a selective neuroprotective agent for dopaminergic neurons with prophylactic and therapeutic potential in PD.

E-MHK-0103 (Mineraxin™): A Novel Nutraceutical with Biological Properties in Menopausal Conditions.

BACKGROUND: Menopause-derived estrogen deprivation and related endocrine factors are linked to some symptoms typical of middle-aged women, such as hot flashes, aches, joint pain, stiffness, depressed mood, bone degeneration, nutritional dysfunction, or difficulty to maintain body mass. Clinical approaches to these problems often involve hormone replacement therapy and other modalities of therapeutic intervention. However, the well-known side effects associated with other pharmacological alternatives have led physicians and patients to pursue new strategies to alleviate these symptoms. As a physiological state, the first recommended option is a natural and healthy therapy, alone or in combination with pharmacotherapy in severe cases. Among other natural alternatives, E-MHK-0103, a nutraceutical lipoprotein extracted from Mytilus galloprovincialis, was found to have beneficial properties. METHODS: We reviewed numerous high-impact references to show the controversies over the current treatments used to alleviate menopausal symptoms, and presented the results obtained with E-MHK-0103 as a good natural alternative. RESULTS: E-MHK-0103 showed positive effects on hot flashes, mood swings, joint pain and bone stability, associated with its glucosamine-related anti-inflammatory effect and its high content of vitamins, minerals, iron and other substances, such as selenium and vitamin E. A significant increase in serum growth hormone, mediated by the hepatic secretion of insulin growth factor-1, and a slight decrease in bone alkaline phosphatase, calcium and ß-crosslaps concentrations contribute to its beneficial impact on bone turnover. E-MHK-0103 also showed a powerful antioxidant effect and an increase in iron stores, of particular importance in women with low basal ferritin levels. CONCLUSION: The findings of this review confirm the efficiency of natural therapies in menopause symptoms, and EMHK- 0103 as a healthy choice for inclusion into clinical practice.