Cargando…
The search for, and chemistry and mechanism of, neurotrophic natural products
ABSTRACT: Neurotrophic factors, now termed neurotrophins, which belong to a class of polypeptidyl agents, have been shown to potentially be beneficial for the treatment of neurodegenerative diseases such as Alzheimer’s disease, because endogenous neurotrophic factors (NGF, BDNF, NT3, NT4) have been...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Singapore
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456418/ https://www.ncbi.nlm.nih.gov/pubmed/32643028 http://dx.doi.org/10.1007/s11418-020-01431-8 |
_version_ | 1783575794912591872 |
---|---|
author | Fukuyama, Yoshiyasu Kubo, Miwa Harada, Kenichi |
author_facet | Fukuyama, Yoshiyasu Kubo, Miwa Harada, Kenichi |
author_sort | Fukuyama, Yoshiyasu |
collection | PubMed |
description | ABSTRACT: Neurotrophic factors, now termed neurotrophins, which belong to a class of polypeptidyl agents, have been shown to potentially be beneficial for the treatment of neurodegenerative diseases such as Alzheimer’s disease, because endogenous neurotrophic factors (NGF, BDNF, NT3, NT4) have been recognized to play critical roles in the promotion of neurogenesis, differentiation, and neuroprotection throughout the development of the central nervous system. However, high-molecular weight proteins are unable to cross the blood–brain barrier and are easily decomposed by peptidase under physiological conditions. To address this issue, small molecules that can mimic the functions of neurotrophic factors would be promising alternatives for the treatment of neurodegenerative disease. We have continued to search for natural products having typical neurotrophic properties, which can cause neurogenesis, enhance neurite outgrowth, and protect neuronal death using three cellular systems (PC12, rat cortical neurons, and MEB5 cells). In this review, we summarize the neurotrophic activities and synthesis of dimeric isocuparane-type sesquiterpenes from the liverwort, Mastigophora diclados, the mechanism of neurotrophic neolignans, magnolol, honokiol and their sesquiterpene derivatives, and introduce unique neurotrophin-mimic natural products, including seco-prezizaane-type sesquiterpenes from the Illicium species, vibsane-type diterpenes from Viburnum awabuki, and miscellaneous natural products with neurotrophic effects discovered by us. GRAPHIC ABSTRACT: [Image: see text] |
format | Online Article Text |
id | pubmed-7456418 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Singapore |
record_format | MEDLINE/PubMed |
spelling | pubmed-74564182020-09-03 The search for, and chemistry and mechanism of, neurotrophic natural products Fukuyama, Yoshiyasu Kubo, Miwa Harada, Kenichi J Nat Med Review ABSTRACT: Neurotrophic factors, now termed neurotrophins, which belong to a class of polypeptidyl agents, have been shown to potentially be beneficial for the treatment of neurodegenerative diseases such as Alzheimer’s disease, because endogenous neurotrophic factors (NGF, BDNF, NT3, NT4) have been recognized to play critical roles in the promotion of neurogenesis, differentiation, and neuroprotection throughout the development of the central nervous system. However, high-molecular weight proteins are unable to cross the blood–brain barrier and are easily decomposed by peptidase under physiological conditions. To address this issue, small molecules that can mimic the functions of neurotrophic factors would be promising alternatives for the treatment of neurodegenerative disease. We have continued to search for natural products having typical neurotrophic properties, which can cause neurogenesis, enhance neurite outgrowth, and protect neuronal death using three cellular systems (PC12, rat cortical neurons, and MEB5 cells). In this review, we summarize the neurotrophic activities and synthesis of dimeric isocuparane-type sesquiterpenes from the liverwort, Mastigophora diclados, the mechanism of neurotrophic neolignans, magnolol, honokiol and their sesquiterpene derivatives, and introduce unique neurotrophin-mimic natural products, including seco-prezizaane-type sesquiterpenes from the Illicium species, vibsane-type diterpenes from Viburnum awabuki, and miscellaneous natural products with neurotrophic effects discovered by us. GRAPHIC ABSTRACT: [Image: see text] Springer Singapore 2020-07-08 2020 /pmc/articles/PMC7456418/ /pubmed/32643028 http://dx.doi.org/10.1007/s11418-020-01431-8 Text en © The Author(s) 2020, corrected publication 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Review Fukuyama, Yoshiyasu Kubo, Miwa Harada, Kenichi The search for, and chemistry and mechanism of, neurotrophic natural products |
title | The search for, and chemistry and mechanism of, neurotrophic natural products |
title_full | The search for, and chemistry and mechanism of, neurotrophic natural products |
title_fullStr | The search for, and chemistry and mechanism of, neurotrophic natural products |
title_full_unstemmed | The search for, and chemistry and mechanism of, neurotrophic natural products |
title_short | The search for, and chemistry and mechanism of, neurotrophic natural products |
title_sort | search for, and chemistry and mechanism of, neurotrophic natural products |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456418/ https://www.ncbi.nlm.nih.gov/pubmed/32643028 http://dx.doi.org/10.1007/s11418-020-01431-8 |
work_keys_str_mv | AT fukuyamayoshiyasu thesearchforandchemistryandmechanismofneurotrophicnaturalproducts AT kubomiwa thesearchforandchemistryandmechanismofneurotrophicnaturalproducts AT haradakenichi thesearchforandchemistryandmechanismofneurotrophicnaturalproducts AT fukuyamayoshiyasu searchforandchemistryandmechanismofneurotrophicnaturalproducts AT kubomiwa searchforandchemistryandmechanismofneurotrophicnaturalproducts AT haradakenichi searchforandchemistryandmechanismofneurotrophicnaturalproducts |