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

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.

Anti-Apoptotic Effects of Carotenoids in Neurodegeneration

“…For example, hydroxyl radical scavenging activity of fucoxanthin is 13.5 times greater than that of α-tocopherol [190]. In addition to scavenging ROS, fucoxanthin may directly occupy the docking site, altering protein function [191]. Fucoxanthin potentially binds directly to amyloid-β, preventing formation of pathological amyloid-β fibril [191].…”

“…In addition to scavenging ROS, fucoxanthin may directly occupy the docking site, altering protein function [191]. Fucoxanthin potentially binds directly to amyloid-β, preventing formation of pathological amyloid-β fibril [191]. Fucoxanthin also regulates intracellular redox status by regulating antioxidant-sensitive genes.…”

Bixin Attenuates Experimental Autoimmune Encephalomyelitis by Suppressing TXNIP/NLRP3 Inflammasome Activity and Activating NRF2 Signaling

“…Bixin is a natural chemo-preventive carotenoid isolated from the seeds of Bixa orellana that is capable of crossing the bloodbrain barrier (14)(15)(16). Bixin is a lineal apocarotenoid of 25 carbon atoms with nine double bonds and has demonstrated various potent pharmacological activities, including antioxidant, anti-inflammatory, and anti-tumor properties (17,18).…”

Protective Effect of Astaxanthin on Ochratoxin A-Induced Kidney Injury to Mice by Regulating Oxidative Stress-Related NRF2/KEAP1 Pathway

“…Studies have shown that ASX has biological activities that include anti-oxidation, anti-tumor, prevention of cardiovascular diseases, improvement of immunity, and coloration [19]. The molecular structure of ASX determines its ability to effectively quench singlet oxygen and scavenge free radicals [20]. ASX has a strong antioxidant activity and is known as a "super antioxidant" [21].…”