Molecular Mechanisms of Astaxanthin as a Potential Neurotherapeutic Agent

Bahbah, Eshak I.; Ghozy, Sherief; Attia, Mohamed S.; Negida, Ahmed; Emran, Talha Bin; Mitra, Saikat; Albadrani, Ghadeer M.; Abdel-Daim, Mohamed M.; Simal-Gándara, Jesús

doi:10.3390/md19040201

Cited by 46 publications

(24 citation statements)

References 141 publications

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“…12). Recent works discuss a plethora of biological effects and applications for xanthophylls, including ZEA, CAN and AXT [60][61][62][63][64][65][66][67][68][69][70][71]. Carotenoid binding and release by CTDH are associated with the oligomeric transition, whereas such activity of AstaP leaves its monomeric state unchanged.…”

Section: Discussionmentioning

confidence: 99%

Microalgal protein AstaP is a potent carotenoid solubilizer and delivery module with a broad carotenoid binding repertoire

Slonimskiy

Egorkin

Friedrich

et al. 2021

Preprint

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Carotenoids are lipophilic substances with many biological functions, from coloration to photoprotection. Being potent antioxidants, carotenoids have multiple biomedical applications, including the treatment of neurodegenerative disorders and retina degeneration. Nevertheless, the delivery of carotenoids is substantially limited by their poor solubility in the aqueous phase. Natural water-soluble carotenoproteins can facilitate this task, necessitating studies on their ability to uptake and deliver carotenoids. One such promising carotenoprotein, AstaP (Astaxanthin-binding protein), was recently identified in eukaryotic microalgae, but its structure and functional properties remained largely uncharacterized. By using a correctly folded recombinant protein, here we show that AstaP is an efficient carotenoid solubilizer that can stably bind not only astaxanthin but also zeaxanthin, canthaxanthin, and, to a lesser extent, β-carotene, i.e. carotenoids especially valuable to human health. AstaP accepts carotenoids provided as acetone solutions or embedded in membranes, forming carotenoid-protein complexes with an apparent stoichiometry of 1:1. We successfully produced AstaP holoproteins in specific carotenoid-producing strains of Escherichia coli, proving it is amenable to cost-efficient biotechnology processes. Regardless of the carotenoid type, AstaP remains monomeric in both apo- and holoforms, while its rather minimalistic mass (∼20 kDa) makes it an especially attractive antioxidant delivery module. In vitro, AstaP transfers different carotenoids to the liposomes and to unrelated proteins from cyanobacteria, which can modulate their photoactivity and/or oligomerization. These findings expand the toolkit of the characterized carotenoid-binding proteins and outline the perspective of the use of AstaP as a unique monomeric antioxidant nanocarrier with an extensive carotenoid-binding repertoire.

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Section: Discussionmentioning

confidence: 99%

Microalgal protein AstaP is a potent carotenoid solubilizer and delivery module with a broad carotenoid binding repertoire

Slonimskiy

Egorkin

Friedrich

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Pharmacologically active substances are extracted from marine organisms, and these substances are developed into suitable forms for use in humans. Indeed, the ocean serves as a source of numerous bioactive substances; however, the ocean is still largely unexploited [ 24 , 25 , 26 , 27 ]. It was revealed through the isolation of soft corals that marine organisms can be an important source for novel drugs containing novel chemical structures and an increased level of therapeutic value.…”

Section: Introductionmentioning

confidence: 99%

Anti-Alzheimer’s Molecules Derived from Marine Life: Understanding Molecular Mechanisms and Therapeutic Potential

et al. 2021

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Alzheimer’s disease (AD) is a devastating neurodegenerative disease and the most common cause of dementia. It has been confirmed that the pathological processes that intervene in AD development are linked with oxidative damage to neurons, neuroinflammation, tau phosphorylation, amyloid beta (Aβ) aggregation, glutamate excitotoxicity, and cholinergic deficit. Still, there is no available therapy that can cure AD. Available therapies only manage some of the AD symptoms at the early stages of AD. Various studies have revealed that bioactive compounds derived from marine organisms and plants can exert neuroprotective activities with fewer adverse events, as compared with synthetic drugs. Furthermore, marine organisms have been identified as a source of novel compounds with therapeutic potential. Thus, there is a growing interest regarding bioactive compounds derived from marine sources that have anti-AD potentials. Various marine drugs including bryostatin-1, homotaurine, anabaseine and its derivative, rifampicins, anhydroexfoliamycin, undecylprodigioisin, gracilins, 13-desmethyl spirolide-C, and dictyostatin displayed excellent bioavailability and efficacy against AD. Most of these marine drugs were found to be well-tolerated in AD patients, along with no significant drug-associated adverse events. In this review, we focus on the drugs derived from marine life that can be useful in AD treatment and also summarize the therapeutic agents that are currently used to treat AD.

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“…12). Recent works discuss a plethora of biological effects and applications for xanthophylls, including ZEA, CAN, and AXT [60][61][62][63][64][65][66][67][68][69][70][71].…”

Section: Discussionmentioning

confidence: 99%

Microalgal protein AstaP is a potent carotenoid solubilizer and delivery module with a broad carotenoid binding repertoire

et al. 2021

View full text Add to dashboard Cite

Carotenoids are lipophilic substances with many biological functions, from coloration to photoprotection. Being potent antioxidants, carotenoids have multiple biomedical applications, including the treatment of neurodegenerative disorders and retina degeneration. Nevertheless, the delivery of carotenoids is substantially limited by their poor solubility in the aqueous phase. Natural water-soluble carotenoproteins can facilitate this task, necessitating studies on their ability to uptake and deliver carotenoids. One such promising carotenoprotein, AstaP (astaxanthin-binding protein), was recently identified in eukaryotic microalgae, but its structure and functional properties remained largely uncharacterized. By using a correctly folded recombinant protein, here we show that AstaP is an efficient carotenoid solubilizer that can stably bind not only astaxanthin but also zeaxanthin, canthaxanthin, and, to a lesser extent, b-carotene, that is, carotenoids especially valuable to human health. AstaP accepts carotenoids provided as acetone solutions or embedded in membranes, forming carotenoid-protein complexes with an apparent stoichiometry of 1:1. We successfully produced AstaP holoproteins in specific carotenoid-producing strains of Escherichia coli, proving it is amenable to cost-efficient biotechnology processes. Regardless of the carotenoid type, AstaP remains monomeric in both apo-and holoform, while its rather minimalistic mass (~20 kDa) makes it an especially attractive antioxidant delivery module. In vitro, AstaP transfers different carotenoids to liposomes and to unrelated proteins from cyanobacteria, which can modulate their photoactivity and/or oligomerization. These findings expand the toolkit of the characterized carotenoid binding proteins and outline the perspective of the use of AstaP as a unique monomeric antioxidant nanocarrier with an extensive carotenoid binding repertoire.

show abstract

Molecular Mechanisms of Astaxanthin as a Potential Neurotherapeutic Agent

Cited by 46 publications

References 141 publications

Microalgal protein AstaP is a potent carotenoid solubilizer and delivery module with a broad carotenoid binding repertoire

Microalgal protein AstaP is a potent carotenoid solubilizer and delivery module with a broad carotenoid binding repertoire

Anti-Alzheimer’s Molecules Derived from Marine Life: Understanding Molecular Mechanisms and Therapeutic Potential

Microalgal protein AstaP is a potent carotenoid solubilizer and delivery module with a broad carotenoid binding repertoire

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