Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Nov 7;20(22):5553.
doi: 10.3390/ijms20225553.

Carotenoids as Novel Therapeutic Molecules Against Neurodegenerative Disorders: Chemistry and Molecular Docking Analysis

Affiliations
Review

Carotenoids as Novel Therapeutic Molecules Against Neurodegenerative Disorders: Chemistry and Molecular Docking Analysis

Johant Lakey-Beitia et al. Int J Mol Sci. .

Abstract

Alzheimer's disease (AD) is the most devastating neurodegenerative disorder that affects the aging population worldwide. Endogenous and exogenous factors are involved in triggering this complex and multifactorial disease, whose hallmark is Amyloid-β (Aβ), formed by cleavage of amyloid precursor protein by β- and γ-secretase. While there is no definitive cure for AD to date, many neuroprotective natural products, such as polyphenol and carotenoid compounds, have shown promising preventive activity, as well as helping in slowing down disease progression. In this article, we focus on the chemistry as well as structure of carotenoid compounds and their neuroprotective activity against Aβ aggregation using molecular docking analysis. In addition to examining the most prevalent anti-amyloidogenic carotenoid lutein, we studied cryptocapsin, astaxanthin, fucoxanthin, and the apocarotenoid bixin. Our computational structure-based drug design analysis and molecular docking simulation revealed important interactions between carotenoids and Aβ via hydrogen bonding and van der Waals interactions, and shows that carotenoids are powerful anti-amyloidogenic molecules with a potential role in preventing AD, especially since most of them can cross the blood-brain barrier and are considered nutraceutical compounds. Our studies thus illuminate mechanistic insights on how carotenoids inhibit Aβ aggregation. The potential role of carotenoids as novel therapeutic molecules in treating AD and other neurodegenerative disorders are discussed.

Keywords: Alzheimer’s disease; Amyloid-β aggregation; apocarotenoid; biosynthesis; carotenoid; molecular docking analysis; structure-activity relationship.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest

Figures

Figure 1
Figure 1
Numeration and biosynthesis of carotenoids: (a) Beta-carotene, capsanthin, and bixin are examples of how carotenoids and apocarotenoid can be numerated; (b) the biosynthesis of carotenoids starts with phytoenes that produce trans- and cis-carotenoids that can produce an epoxy carotenoid and finally an apocarotenoid.
Figure 2
Figure 2
Biosynthesis of carotenoids and their five crucial reactions: desaturation (1), cyclization (2), hydroxylation (3), epoxidation (4), and epoxide-furanoxide rearrangement (5).
Figure 3
Figure 3
Examples of structures of some of the apocarotenoids.
Figure 4
Figure 4
Desaturation and cyclization reaction.
Figure 5
Figure 5
Hydroxylation, epoxidation, and epoxide-furanoide rearrangement reactions.
Figure 6
Figure 6
Types of carotenoid derivatives.
Figure 7
Figure 7
The Protein Data Bank (PDB) structures of four selected forms of Aβ fibrils are: (a) 2BEG including the Aβ17–42 region; (b) 2MXU is characterized by the Aβ11–42 region; (c) 2NAO is conformed by the Aβ1–42 region; (d) 2M4J contains the Aβ1–40 region.
Figure 8
Figure 8
Probable receptor binding sites and alternative binding regions across different Aβ fibrils where ligand binding interactions can occur. Red dots correspond to the amino acid in the binding site.
Figure 9
Figure 9
Hypothetical model of inhibition of Aβ aggregation by carotenoids and apocarotenoids. In this hypothetical inhibition of Aβ aggregation, lutein, a carotenoid with non-pro-vitamin A, showed the higher inhibition follow by cryptocapsin, a carotenoid with pro-vitamin A. After, astaxanthin and fucoxanthin, both of them are carotenoids with non-pro-vitamin A, and finally, Bixin, apocatenoid without pro-vitamin A.
Figure 10
Figure 10
The hypothetical model to understand the role of carotenoids in the inhibition of Aβ42 formation. β- and γ-secretases are the two enzymes that cleavage the amyloid precursor protein (APP) to form Aβ peptide. The aggregation of this peptide pass to dimer follows to oligomer until Aβ fibril. Carotenoids may potentially inhibit the APP pathway where carotenoids have been demonstrated to inhibit Aβ dimer, also oligomer, and also the disaggregation of Aβ fibril. Color code: Aβ (yellow), carotenoid (red), β-secretase (brown) and γ-secretase (green).

Similar articles

Cited by

References

    1. Hashimoto M., Rockenstein E., Crews L., Masliah E. Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer’s and Parkinson’s diseases. Neuromol. Med. 2003;4:21–36. doi: 10.1385/NMM:4:1-2:21. - DOI - PubMed
    1. Prado-Prado F., García I. Review of theoretical studies for prediction of neurodegenerative inhibitors. Mini Rev. Med. Chem. 2012;12:452–466. doi: 10.2174/138955712800493780. - DOI - PubMed
    1. Cho J.K., Ryu Y.B., Curtis-Long M.J., Ryu H.W., Yuk H.J., Kim D.W., Kim H.J., Lee W.S., Park K.H. Cholinestrase inhibitory effects of geranylated flavonoids from Paulownia tomentosa fruits. Bioorg. Med. Chem. 2012;20:2595–2602. doi: 10.1016/j.bmc.2012.02.044. - DOI - PubMed
    1. Majd S., Power J.H., Grantham H.J.M. Neuronal response in Alzheimer’s and Parkinson’s disease: The effect of toxic proteins on intracellular pathways. BMC Neurosci. 2015;16:69. doi: 10.1186/s12868-015-0211-1. - DOI - PMC - PubMed
    1. Wang S.S., Hung Y.T., Wen W.S., Lin K.C., Chen G.Y. Exploring the inhibitory activity of short-chain phospholipids against amyloid fibrillogenesis of hen egg-white lysozyme. Biochim. Biophys. Acta. 2011;1811:301–313. doi: 10.1016/j.bbalip.2011.02.003. - DOI - PubMed

MeSH terms