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The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington’s Disease
Huntington’s disease (HD) is a rare and fatal neurodegenerative disorder with no disease-modifying therapeutics. HD is characterized by extensive neuronal loss and is caused by the inherited expansion of the huntingtin (HTT) gene that encodes a toxic mutant HTT (mHTT) protein having expanded polyglu...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Bentham Science Publishers
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227909/ https://www.ncbi.nlm.nih.gov/pubmed/36797612 http://dx.doi.org/10.2174/1570159X21666230216104621 |
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author | Bhat, Shahnawaz Ali Ahamad, Shakir Dar, Nawab John Siddique, Yasir Hassan Nazir, Aamir |
author_facet | Bhat, Shahnawaz Ali Ahamad, Shakir Dar, Nawab John Siddique, Yasir Hassan Nazir, Aamir |
author_sort | Bhat, Shahnawaz Ali |
collection | PubMed |
description | Huntington’s disease (HD) is a rare and fatal neurodegenerative disorder with no disease-modifying therapeutics. HD is characterized by extensive neuronal loss and is caused by the inherited expansion of the huntingtin (HTT) gene that encodes a toxic mutant HTT (mHTT) protein having expanded polyglutamine (polyQ) residues. Current HD therapeutics only offer symptomatic relief. In fact, Food and Drug Administration (FDA) approved two synthetic small-molecule VMAT2 inhibitors, tetrabenazine (1) and deutetrabenazine (2), for managing HD chorea and various other diseases in clinical trials. Therefore, the landscape of drug discovery programs for HD is evolving to discover disease-modifying HD therapeutics. Likewise, numerous natural products are being evaluated at different stages of clinical development and have shown the potential to ameliorate HD pathology. The inherent anti-inflammatory and antioxidant properties of natural products mitigate the mHTT-induced oxidative stress and neuroinflammation, improve mitochondrial functions, and augment the anti-apoptotic and pro-autophagic mechanisms for increased survival of neurons in HD. In this review, we have discussed HD pathogenesis and summarized the anti-HD clinical and pre-clinical natural products, focusing on their therapeutic effects and neuroprotective mechanism/s. |
format | Online Article Text |
id | pubmed-10227909 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Bentham Science Publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-102279092023-10-11 The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington’s Disease Bhat, Shahnawaz Ali Ahamad, Shakir Dar, Nawab John Siddique, Yasir Hassan Nazir, Aamir Curr Neuropharmacol Medicine, Neurology, Pharmacology, Neuroscience Huntington’s disease (HD) is a rare and fatal neurodegenerative disorder with no disease-modifying therapeutics. HD is characterized by extensive neuronal loss and is caused by the inherited expansion of the huntingtin (HTT) gene that encodes a toxic mutant HTT (mHTT) protein having expanded polyglutamine (polyQ) residues. Current HD therapeutics only offer symptomatic relief. In fact, Food and Drug Administration (FDA) approved two synthetic small-molecule VMAT2 inhibitors, tetrabenazine (1) and deutetrabenazine (2), for managing HD chorea and various other diseases in clinical trials. Therefore, the landscape of drug discovery programs for HD is evolving to discover disease-modifying HD therapeutics. Likewise, numerous natural products are being evaluated at different stages of clinical development and have shown the potential to ameliorate HD pathology. The inherent anti-inflammatory and antioxidant properties of natural products mitigate the mHTT-induced oxidative stress and neuroinflammation, improve mitochondrial functions, and augment the anti-apoptotic and pro-autophagic mechanisms for increased survival of neurons in HD. In this review, we have discussed HD pathogenesis and summarized the anti-HD clinical and pre-clinical natural products, focusing on their therapeutic effects and neuroprotective mechanism/s. Bentham Science Publishers 2023-03-30 2023-03-30 /pmc/articles/PMC10227909/ /pubmed/36797612 http://dx.doi.org/10.2174/1570159X21666230216104621 Text en © 2023 Bentham Science Publishers https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited. |
spellingShingle | Medicine, Neurology, Pharmacology, Neuroscience Bhat, Shahnawaz Ali Ahamad, Shakir Dar, Nawab John Siddique, Yasir Hassan Nazir, Aamir The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington’s Disease |
title | The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington’s Disease |
title_full | The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington’s Disease |
title_fullStr | The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington’s Disease |
title_full_unstemmed | The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington’s Disease |
title_short | The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington’s Disease |
title_sort | emerging landscape of natural small-molecule therapeutics for huntington’s disease |
topic | Medicine, Neurology, Pharmacology, Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227909/ https://www.ncbi.nlm.nih.gov/pubmed/36797612 http://dx.doi.org/10.2174/1570159X21666230216104621 |
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