Complexity of dopamine metabolism

TLDR

Parkinson’s disease is marked by a dramatic loss of substantia nigra dopaminergic neurons, a process driven in part by oxidative stress generated during dopamine metabolism, which produces reactive oxygen species and neurotoxic derivatives while some metabolites exhibit antioxidant properties. The review aims to provide a comprehensive overview of dopamine metabolism—including biosynthesis, sequestration, degradation, oxidation chemistry, and regulation of involved enzymes—to better understand its role in neuronal redox homeostasis and Parkinson’s disease, and to explore medical implications. The authors examine dopamine biosynthesis, sequestration, degradation, oxidation chemistry, and the transcriptional, translational, and posttranslational regulation of its enzymes, and summarize cellular models used in Parkinson’s disease research.

Abstract

: Parkinson's disease (PD) coincides with a dramatic loss of dopaminergic neurons within the substantia nigra. A key player in the loss of dopaminergic neurons is oxidative stress. Dopamine (DA) metabolism itself is strongly linked to oxidative stress as its degradation generates reactive oxygen species (ROS) and DA oxidation can lead to endogenous neurotoxins whereas some DA derivatives show antioxidative effects. Therefore, DA metabolism is of special importance for neuronal redox-homeostasis and viability.In this review we highlight different aspects of dopamine metabolism in the context of PD and neurodegeneration. Since most reviews focus only on single aspects of the DA system, we will give a broader overview by looking at DA biosynthesis, sequestration, degradation and oxidation chemistry at the metabolic level, as well as at the transcriptional, translational and posttranslational regulation of all enzymes involved. This is followed by a short overview of cellular models currently used in PD research. Finally, we will address the topic from a medical point of view which directly aims to encounter PD.