Neuroprotective Potential of Crustacean-Derived Astaxanthin: A Review on Monoamine Oxidase Inhibition
Abstract
Monoamine oxidases (MAO-A and MAO-B) are critical flavin-dependent enzymes anchored to the outer mitochondrial membrane, responsible for the oxidative deamination of biogenic amines; however, their catalytic activity generates neurotoxic by-products, including hydrogen peroxide and reactive aldehydes, which contribute to the pathogenesis of Alzheimer’s and Parkinson’s diseases. While the valorization of shrimp-processing by-products (accounting for 50–60% of total landing biomass) represents an important pillar of the circular bioeconomy, their principal bioactive carotenoid, astaxanthin (AST), is widely investigated for its neuroprotective and antioxidant attributes. This critical review evaluates the mechanistic pathways through which AST mitigates neurotoxicity, with an analytical focus on its proposed, isoform-selective interactions with monoamine oxidases. Current computational docking evidence suggests that unesterified AST possesses spatial compatibility with the substrate-binding cavity of MAO-A, whereas steric hindrance prevents its accommodation within the narrow, bipartite channel of MAO-B. However, direct experimental verification such as recombinant enzyme kinetics, Ki and IC50 determinations, and cellular inhibition assays remains largely absent in the literature. Furthermore, native crustacean extracts predominantly consist of fatty-acid-esterified stereoisomers rather than the unesterified free form modeled in silico, presenting structural differences that could influence active-site entry. This review outlines the literature retrieval methodology, critically appraises verified downstream neuroprotective mechanisms (including Nrf2/HO-1 upregulation, lipid peroxidation attenuation, and mitochondrial membrane stabilization), and contrasts theoretical binding predictions against established empirical benchmarks. Existing literature gaps, discrepancies between purified standards and crude by-product extracts, and the empirical validations necessary before AST can be considered a reliable MAO-modulating candidate are discussed.
Keywords
Astaxanthin, Circular bioeconomy, Molecular docking, Monoamine oxidase, Neuroprotection, Shrimp waste
Ethical Statement
Thanks
References
- Abdol Wahab, N. R., Meor Mohd Affandi, M. M. R., Fakurazi, S., Alias, E., & Hassan, H. (2022). Nanocarrier system: State-of-the-art in oral delivery of astaxanthin. Antioxidants, 11(9), 1676. https://doi.org/10.3390/antiox11091676
- Akwu, N. A., Lekhooa, M., Deqiang, D., & Aremu, A. O. (2023). Antidepressant effects of coumarins and their derivatives: A critical analysis of research advances. European Journal of Pharmacology, 956, 175958. https://doi.org/10.1016/j.ejphar.2023.175958
- Ali, S. M., Appolloni, A., Cavallaro, F., D’Adamo, I., Di Vaio, A., Ferella, F., ... & Zorpas, A. A. (2023). Development goals towards sustainability. Sustainability, 15(12), 9443. https://doi.org/10.3390/su15129443
- Ambati, R. R., Phang, S. M., Ravi, S., & Aswathanarayana, R. G. (2014). Astaxanthin: Sources, extraction, stability, biological activities and its commercial applications—A review. Marine Drugs, 12(1), 128-152. https://doi.org/10.3390/md12010128
- Bahbah, E. I., Ghozy, S., Attia, M. S., Negida, A., Emran, T. B., Mitra, S., Albadrani, G. M., Abdel-Daim, M. M., Uddin, Md. S., & Simal-Gandara, J. (2021). Molecular mechanisms of astaxanthin as a potential neurotherapeutic agent. Marine Drugs, 19(4), 201. https://doi.org/10.3390/md19040201
- Burke, W. J., Kumar, V. B., Pandey, N., Panneton, W. M., Gan, Q., Franko, M. W., O’Dell, M., Li, S. W., Pan, Y., Chung, H. D., & Galvin, J. E. (2008). Aggregation of α-synuclein by DOPAL, the monoamine oxidase metabolite of dopamine. Acta Neuropathologica, 115(2), 193-203. https://doi.org/10.1007/s00401-007-0303-9
- Cao, Y., Yang, L., Qiao, X., Xue, C., & Xu, J. (2023). Dietary astaxanthin: An excellent carotenoid with multiple health benefits. Critical Reviews in Food Science and Nutrition, 63(18), 3019-3045. https://doi.org/10.1080/10408398.2021.1983766
- Capelli, B., Bagchi, D., & Cysewski, G. R. (2013). Synthetic astaxanthin is significantly inferior to algal-based astaxanthin as an antioxidant and may not be suitable as a human nutraceutical supplement. Nutrafoods, 12(4),145-152. https://doi.org/10.1007/s13749-013-0051-5
- Catanzaro, E., Bishayee, A., & Fimognari, C. (2020). On a beam of light: Photoprotective activities of the marine carotenoids astaxanthin and fucoxanthin in suppression of inflammation and cancer. Marine Drugs, 18(11), 544. https://doi.org/10.3390/md18110544
- Chi Hai, T., Van Man, P., & Anh, L. T. H. (2025). Microwave-assisted extraction of astaxanthin from shrimp shell by-products (Penaeus monodon) using deep eutectic solvents and evaluation of antioxidant activity. Journal of Food Measurement and Characterization, 19(7), 4796-4811. https://doi.org/10.1007/s11694-025-03292-9