Use of galantamine in the treatment of Alzheimer's disease and strategies to optimize its biosynthesis using the in vitr
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REVIEW
Use of galantamine in the treatment of Alzheimer’s disease and strategies to optimize its biosynthesis using the in vitro culture technique Gabriella Sousa Santos1 · Simone Batista Pires Sinoti1 · Fabrício Tavares Cunha de Almeida2 · Dâmaris Silveira1 · Luiz Alberto Simeoni1 · Kicia Karinne Pereira Gomes‑Copeland1 Received: 27 February 2020 / Accepted: 9 August 2020 © Springer Nature B.V. 2020
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. Keywords Alzheimer disease · Amaryllidaceae · Biosynthesis · Galantamine · Plant tissue culture · In vitro cultivation strategies
Communicated by Nokwanda Pearl Makunga. * Gabriella Sousa Santos [email protected] * Kicia Karinne Pereira Gomes‑Copeland [email protected] 1
Faculty of Health Sciences, University of Brasília, Darcy Ribeiro University Campus, Federal District, Brasília, CEP 70910‑900, Brazil
Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina
2
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
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