Exploiting Principal Component Analysis (PCA) to reveal temperature, buffer and metal ions' role in neuromelanin (NM) synthesis by dopamine (DA) oxidative polymerization
- PMID: 38593610
- DOI: 10.1016/j.jinorgbio.2024.112548
Exploiting Principal Component Analysis (PCA) to reveal temperature, buffer and metal ions' role in neuromelanin (NM) synthesis by dopamine (DA) oxidative polymerization
Abstract
Neuromelanin (NM) plays a well-established role in neurological disorders pathogenesis; the mechanism of action is still discussed and the investigations in this field are limited by NM's complex and heterogeneous composition, insolubility, and low availability from human brains. An alternative can be offered by synthetic NM obtained from dopamine (DA) oxidative polymerization; however, a deep knowledge of the influence of both physicochemical parameters (T, pH, ionic strength) and other compounds in the reaction media (buffer, metal ions, other catecholamines) on DA oxidation process and, consequently, on synthetic NM features is mandatory to develop reliable NM preparation methodologies. To partially fulfill this aim, the present work focuses on defining the role of temperature, buffer and metal ions on both DA oxidation rate and DA oligomer size. DA oxidation in the specific conditions is monitored by UV-Vis spectroscopy and Principal Component Analysis (PCA) is run either on the raw spectra to model the background absorption increase, related to small DA oligomers formation, or on their first derivative to rationalize DA consumption. After having studied three case studies, 3-Way PCA is applied to directly evaluate the effect of temperature and buffer type on DA oxidation in the presence of different metal ions. Despite the proof-of-concept nature of the work and the number of compounds still to be included in the investigation, the preliminary results and the possibility to further expand the chemometric approach represent an interesting contribution to the field of in vitro simulation of NM synthesis.
Keywords: 3-WAY PCA; Chemometrics; Dopamine oxidation; Neurological disorders pathogenesis; PCA; Synthetic neuromelanin.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest 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.
Similar articles
-
Biosynthetic pathway to neuromelanin and its aging process.Pigment Cell Melanoma Res. 2012 Nov;25(6):792-803. doi: 10.1111/pcmr.12014. Epub 2012 Oct 1. Pigment Cell Melanoma Res. 2012. PMID: 22938712
-
Modulation by neuromelanin of the availability and reactivity of metal ions.Ann Neurol. 1992;32 Suppl:S69-75. doi: 10.1002/ana.410320712. Ann Neurol. 1992. PMID: 1510383 Review.
-
Iron and copper ions accelerate and modify dopamine oxidation to eumelanin: implications for neuromelanin genesis.J Neural Transm (Vienna). 2023 Jan;130(1):29-42. doi: 10.1007/s00702-022-02574-6. Epub 2022 Dec 17. J Neural Transm (Vienna). 2023. PMID: 36527527
-
Iron species-mediated dopamine oxidation, proteasome inhibition, and dopaminergic cell demise: implications for iron-related dopaminergic neuron degeneration.Free Radic Biol Med. 2010 Dec 15;49(12):1856-71. doi: 10.1016/j.freeradbiomed.2010.09.010. Epub 2010 Sep 18. Free Radic Biol Med. 2010. PMID: 20854902
-
Impact of Dopamine Oxidation on Dopaminergic Neurodegeneration.ACS Chem Neurosci. 2019 Feb 20;10(2):945-953. doi: 10.1021/acschemneuro.8b00454. Epub 2019 Jan 17. ACS Chem Neurosci. 2019. PMID: 30592597 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources