To what extent may aminochrome increase the vulnerability of dopaminergic neurons in the context of Parkinson’s disease
The International Journal of Biochemistry & Cell Biology. 2024-03-01; 168: 106528
DOI: 10.1016/j.biocel.2024.106528
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1. Int J Biochem Cell Biol. 2024 Mar;168:106528. doi:
10.1016/j.biocel.2024.106528. Epub 2024 Jan 19.
To what extent may aminochrome increase the vulnerability of dopaminergic
neurons in the context of Parkinson’s disease.
Chagraoui A(1), Anouar Y(2), De Deurwaerdere P(3), Arias HR(4).
Author information:
(1)Department of Medical Biochemistry, Rouen University Hospital, CHU de Rouen,
France; UNIROUEN, Inserm U1239, Neuroendocrine, Endocrine and Germinal
Differentiation and Communication (NorDiC), Rouen Normandie University, 76000
Mont-Saint-Aignan, France. Electronic address: .
(2)UNIROUEN, Inserm U1239, Neuroendocrine, Endocrine and Germinal
Differentiation and Communication (NorDiC), Rouen Normandie University, 76000
Mont-Saint-Aignan, France.
(3)Centre National de la Recherche Scientifique, Institut des Neurosciences
Intégratives et Cognitives d’Aquitaine, UMR, 5287, Bordeaux, France.
(4)Department of Pharmacology and Physiology, Oklahoma State University College
of Osteopathic Medicine, Tahlequah, OK, USA.
Parkinson’s disease (PD) is a neurodegenerative disorder that progresses over
time and is characterized by preferential reduction of dopaminergic neurons in
the substantia nigra. Although the precise mechanisms leading to cell death in
neurodegenerative disorders, such as PD, are not fully understood, it is widely
accepted that increased oxidative stress may be a prevalent factor contributing
to the deterioration of the nigrostriatal dopaminergic fibers in such
conditions. Aminochrome, generated from dopamine (DA) metabolism, plays an
important role in multiple pathogenic mechanisms associated with PD. Its
capacity to induce a gradual reduction in dopaminergic neurons is due to its
endogenous neurotoxicity. The formation of aminochrome results in the production
of various reactive oxygen species (ROS), including pro-inflammatory factors,
superoxide, nitric oxide, and hydroxyl radicals. This, in turn, causes loss of
dopaminergic neurons, reducing DA uptake, and reduced numbers and shortened
dendrites. Notably, o-quinones, which are more cytotoxic, arise from the
oxidation of DA and possess a higher capacity to impede cellular defense
mechanisms, thereby resulting in the death of neuronal cells. Aminochrome
potentially contributes to the pathophysiology of PD by forming adducts with
various proteins. All of the aforementioned effects suggest that aminochrome may
play a crucial role in the pathophysiology of PD. Thus, aminochrome may serve as
a more relevant preclinical model for PD, facilitating a better understanding of
its pathophysiological processes and identification of novel therapeutic
strategies aimed at preventing or slowing disease progression.
Copyright © 2024 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.biocel.2024.106528
PMID: 38246261 [Indexed for MEDLINE]
Conflict of interest statement: Declaration of Competing Interest All authors
have made substantial contributions to the preparation of the manuscript.
Furthermore, they have not only contributed to the writing of the final
manuscript but have given their permission for submission and publication in
European Journal of Pharmacology. The authors declare that they have no known
competing financial interests or personal relationships that could have appeared
to influence the work reported in this paper.