Abstract
Galantamine is an alkaloid in the Amaryllidaceae family widely used in the treatment of Alzheimer's disease. Since its approval for clinical use in 2001, its effectiveness has been attested in numerous clinical trials. Due to the expressive and growing increase in Alzheimer's disease cases in the world, driven by the increase in life expectancy, the main risk factor for neurodegenerative diseases, demand for galantamine is expected to be intensified, this aggravating factor has encouraged researchers to seek viable alternatives for the commercialization of galantamine on a larger scale. However, due to its complex stereochemistry, the organic synthesis of galantamine proved to be a challenging task, thus constituting plants as its main source of production. In this sense, biotechnological techniques have emerged as an alternative and a more efficient means, since plants biosynthesize galantamine and other alkaloids without difficulty. This review summarizes the results of studies on the tools currently available in plant tissue culture capable of optimizing galantamine production aiming at large scale production for the treatment of Alzheimer's disease. Results of galantamine biosynthesis optimization from the use of biotic and abiotic elicitors, plants growth regulators, phytoregulator and precursors agents or intermediate components, endorse the clinical importance of galantamine in the treatment of Alzheimer's disease and the role of in vitro cultivation technique as an environmentally sustainable culture, are discussed.
Key message
Biotechnological strategies can optimize the biosynthesis of galantamine in vitro for treating Alzheimer’s disease, such as the use of elicitors, plant growth regulators, precursor agents, besides be a technique environmentally sustainable.
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Abbreviations
- 2,4-D:
-
2,4-Dichlorophenoxyacetic acid
- AA:
-
Arachidonic acid
- Aβ:
-
Amyloid β-protein
- ACh:
-
Acetylcholine
- AChE:
-
Acetylcholinesterase
- AD:
-
Alzheimer disease
- ANVISA:
-
The Brazilian Health Surveillance Agency
- BA:
-
6-Benzyladenine
- BAP:
-
Benzylaminopurine
- CHI:
-
Chitosan
- DW:
-
Dry weight
- FDA:
-
Food and drug administration
- FW:
-
Fresh weight
- GAL:
-
Galantamine
- G.D.P.:
-
Gross domestic product
- IUCN:
-
International Union for Conservation of Nature
- Melatonin::
-
(N-acetyl-5-methoxy tryptamine)
- MJ:
-
Methyl jasmonate
- MS:
-
Murashige and skoog basal medium
- NAA:
-
Naphthalene-1-acetic acid
- NFNGAL:
-
N-formylnorgalantamine
- NpN4OMT:
-
Norbelladine 4-O-methyltransferase
- PAL:
-
Phenylalanine ammonia lyase
- PGRs:
-
Plant growth regulators
- Picloram:
-
4-Amino-3,5,6-trichloro picolinic acid
- SA:
-
Salicylic acid
- TAZ:
-
Tazettine
- TD:
-
Tyrosine decarboxylase
- Zeatin:
-
6-(4-Hydroxy-3-methylbut-2-enylamino purine
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The authors are grateful to the University of Brasilia for providing the facilities to carry out this work and, to financing in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001, CNPq and FAPDF, for the support and scholarships.
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Santos, G.S., Sinoti, S.B.P., de Almeida, F.T.C. et al. Use of galantamine in the treatment of Alzheimer's disease and strategies to optimize its biosynthesis using the in vitro culture technique. Plant Cell Tiss Organ Cult 143, 13–29 (2020). https://doi.org/10.1007/s11240-020-01911-5
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DOI: https://doi.org/10.1007/s11240-020-01911-5