Tetrahydrobioterin (BH4) pathway: from metabolism to neuropsychiatry
| Autor: | Frédéric Calon, Hortense Fanet, Sylvie Vancassel, Lucile Capuron, N Castanon |
|---|---|
| Přispěvatelé: | Département d'Electronique, des Détecteurs et d'Informatique pour la Physique (ex SEDI) (DEDIP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Laval [Québec] (ULaval) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Serotonin GTP cyclohydrolase I [SDV]Life Sciences [q-bio] Inflammation guanosine-triphosphate-cyclohydrolase-1 (GCH1) Pharmacology medicine.disease_cause Nitric Oxide Article Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine monoamines Dopamine Monoaminergic medicine Glucose homeostasis Humans Pharmacology (medical) Parkinson GTP Cyclohydrolase biology Chemistry cofactor Alzhemier General Medicine Neuropsychiatry Biopterin 3. Good health Psychiatry and Mental health 030104 developmental biology Monoamine neurotransmitter Neurology tetrahydrobiopterin (BH4) depression biology.protein Neurology (clinical) medicine.symptom 030217 neurology & neurosurgery Oxidative stress medicine.drug |
| Zdroj: | Current Neuropharmacology Current Neuropharmacology, Bentham Science Publishers, 2021, 19 (5), pp.591-609. ⟨10.2174/1570159X18666200729103529⟩ Current Neuropharmacology, 2021, 19 (5), pp.591-609. ⟨10.2174/1570159X18666200729103529⟩ |
| ISSN: | 1570-159X |
| DOI: | 10.2174/1570159X18666200729103529⟩ |
| Popis: | Tetrahydrobipterin (BH4) is a pivotal enzymatic cofactor required for the synthesis of serotonin, dopamine and nitric oxide. BH4 is essential for numerous physiological processes at periphery and central levels, such as vascularization, inflammation, glucose homeostasis, regulation of oxidative stress and neurotransmission. BH4 de novo synthesis involves the sequential activation of three enzymes, the major controlling point being GTP cyclohydrolase I (GCH1). Complementary salvage and recycling pathways ensure that BH4 levels are tightly kept within a physiological range in the body. Even if the way of transport of BH4 and its ability to enter the brain after peripheral administration is still controversial, data showed increased levels in the brain after BH4 treatment. Available evidence shows that GCH1 expression and BH4 synthesis are stimulated by immunological factors, notably pro-inflammatory cytokines. Once produced, BH4 can act as an anti- inflammatory molecule and scavenger of free radicals protecting against oxidative stress. At the same time, BH4 is prone to autoxidation, leading to the release of superoxide radicals contributing to inflammatory processes, and to the production of BH2, an inactive form of BH4, reducing its bioavailability. Alterations in BH4 levels have been documented in many pathological situations, including Alzheimer's disease, Parkinson's disease and depression, in which increased oxidative stress, inflammation and alterations in monoaminergic function are described. This review aims at providing an update of the knowledge about metabolism and the role of BH4 in brain function, from preclinical to clinical studies, addressing some therapeutic implications. |
| Databáze: | OpenAIRE |
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