Human DOPA Decarboxylase in Monoamine Metabolism, Pharmacology, and Synucleinopathies.
- 1Department of Medicine and Surgery, University of Perugia, Piazza Lucio Severi 1, 06132 Perugia, Italy.
- 2Department of Life Science, Health, and Health Professions, Link Campus University, Via del Casale di San Pio V 44, 00165 Rome, Italy.
Abstract
Human DOPA decarboxylase is the pyridoxal 5'-phosphate-dependent enzyme that produces dopamine and serotonin. For most of its history it has been treated as a constitutive downstream step rather than a point of regulation, and it has received correspondingly little mechanistic attention. The human enzyme is broadly expressed across central monoaminergic neurons and peripheral neuroendocrine tissues, where it operates in different chemical environments and under different pharmacological constraints. Structurally, it interconverts between an open, cofactor-free apo-form and a closed, catalytically competent holo-form, with conformational dynamics that extend well beyond the active site. Its activity is further tuned by cofactor availability, by phosphorylation, and by protein partners, of which the most notable is α-synuclein Its effect on the enzyme is documented in cellular systems but still unresolved at the molecular level. Pharmacologically, carbidopa is its principal peripheral inhibitor, but its mechanism remains incompletely characterized, and chronic therapy raises rather than lowers circulating AADC levels. In parallel, AADC measured in cerebrospinal fluid has emerged as one of the most discriminating fluid biomarkers for Parkinson's disease and dementia with Lewy bodies, with changes detectable years before motor onset. These different layers, structural, regulatory, pharmacological, and diagnostic, converge on a single enzyme whose biology has long been treated as settled, and which is now being reevaluated as a fundamental node in the molecular landscape of synucleinopathies.
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BibTeX
@article{chiasserini2026human,
title = {{Human DOPA Decarboxylase in Monoamine Metabolism, Pharmacology, and Synucleinopathies.}},
author = {Davide Chiasserini and Giovanni Bellomo and Pier Luigi Orvietani and Mirco Dindo},
journal = {ACS bio \& med chem Au},
year = {2026},
month = aug,
doi = {10.1021/acsbiomedchemau.6c00141},
url = {https://europepmc.org/article/MED/42921305},
note = {CC BY},
}
RIS
TY - JOUR
TI - Human DOPA Decarboxylase in Monoamine Metabolism, Pharmacology, and Synucleinopathies.
AU - Davide Chiasserini
AU - Giovanni Bellomo
AU - Pier Luigi Orvietani
AU - Mirco Dindo
PY - 2026
DA - 2026/08/26
JO - ACS bio & med chem Au
DO - 10.1021/acsbiomedchemau.6c00141
UR - https://europepmc.org/article/MED/42921305
AB - Human DOPA decarboxylase is the pyridoxal 5'-phosphate-dependent enzyme that produces dopamine and serotonin. For most of its history it has been treated as a constitutive downstream step rather than a point of regulation, and it has received correspondingly little mechanistic attention. The human enzyme is broadly expressed across central monoaminergic neurons and peripheral neuroendocrine tissues, where it operates in different chemical environments and under different pharmacological constraints. Structurally, it interconverts between an open, cofactor-free apo-form and a closed, catalytically competent holo-form, with conformational dynamics that extend well beyond the active site. Its activity is further tuned by cofactor availability, by phosphorylation, and by protein partners, of which the most notable is α-synuclein Its effect on the enzyme is documented in cellular systems but still unresolved at the molecular level. Pharmacologically, carbidopa is its principal peripheral inhibitor, but its mechanism remains incompletely characterized, and chronic therapy raises rather than lowers circulating AADC levels. In parallel, AADC measured in cerebrospinal fluid has emerged as one of the most discriminating fluid biomarkers for Parkinson's disease and dementia with Lewy bodies, with changes detectable years before motor onset. These different layers, structural, regulatory, pharmacological, and diagnostic, converge on a single enzyme whose biology has long been treated as settled, and which is now being reevaluated as a fundamental node in the molecular landscape of synucleinopathies.
SN - 2694-2437
ER -