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Neuroprotective Effects of a Small Mitochondrially-Targeted Tetrapeptide Elamipretide in Neurodegeneration
Neural mitochondrial dysfunction, neural oxidative stress, chronic neuroinflammation, toxic protein accumulation, and neural apoptosis are common causes of neurodegeneration. Elamipretide, a small mitochondrially-targeted tetrapeptide, exhibits therapeutic effects and safety in several mitochondria-...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801496/ https://www.ncbi.nlm.nih.gov/pubmed/35111001 http://dx.doi.org/10.3389/fnint.2021.747901 |
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author | Nhu, Nguyen Thanh Xiao, Shu-Yun Liu, Yijie Kumar, V. Bharath Cui, Zhen-Yang Lee, Shin-Da |
author_facet | Nhu, Nguyen Thanh Xiao, Shu-Yun Liu, Yijie Kumar, V. Bharath Cui, Zhen-Yang Lee, Shin-Da |
author_sort | Nhu, Nguyen Thanh |
collection | PubMed |
description | Neural mitochondrial dysfunction, neural oxidative stress, chronic neuroinflammation, toxic protein accumulation, and neural apoptosis are common causes of neurodegeneration. Elamipretide, a small mitochondrially-targeted tetrapeptide, exhibits therapeutic effects and safety in several mitochondria-related diseases. In neurodegeneration, extensive studies have shown that elamipretide enhanced mitochondrial respiration, activated neural mitochondrial biogenesis via mitochondrial biogenesis regulators (PCG-1α and TFAM) and the translocate factors (TOM-20), enhanced mitochondrial fusion (MNF-1, MNF-2, and OPA1), inhibited mitochondrial fission (Fis-1 and Drp-1), as well as increased mitophagy (autophagy of mitochondria). In addition, elamipretide has been shown to attenuate neural oxidative stress (hydrogen peroxide, lipid peroxidation, and ROS), neuroinflammation (TNF, IL-6, COX-2, iNOS, NLRP3, cleaved caspase-1, IL-1β, and IL-18), and toxic protein accumulation (Aβ). Consequently, elamipretide could prevent neural apoptosis (cytochrome c, Bax, caspase 9, and caspase 3) and enhance neural pro-survival (Bcl2, BDNF, and TrkB) in neurodegeneration. These findings suggest that elamipretide may prevent the progressive development of neurodegenerative diseases via enhancing mitochondrial respiration, mitochondrial biogenesis, mitochondrial fusion, and neural pro-survival pathway, as well as inhibiting mitochondrial fission, oxidative stress, neuroinflammation, toxic protein accumulation, and neural apoptosis. Elamipretide or mitochondrially-targeted peptide might be a targeted agent to attenuate neurodegenerative progression. |
format | Online Article Text |
id | pubmed-8801496 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88014962022-02-01 Neuroprotective Effects of a Small Mitochondrially-Targeted Tetrapeptide Elamipretide in Neurodegeneration Nhu, Nguyen Thanh Xiao, Shu-Yun Liu, Yijie Kumar, V. Bharath Cui, Zhen-Yang Lee, Shin-Da Front Integr Neurosci Integrative Neuroscience Neural mitochondrial dysfunction, neural oxidative stress, chronic neuroinflammation, toxic protein accumulation, and neural apoptosis are common causes of neurodegeneration. Elamipretide, a small mitochondrially-targeted tetrapeptide, exhibits therapeutic effects and safety in several mitochondria-related diseases. In neurodegeneration, extensive studies have shown that elamipretide enhanced mitochondrial respiration, activated neural mitochondrial biogenesis via mitochondrial biogenesis regulators (PCG-1α and TFAM) and the translocate factors (TOM-20), enhanced mitochondrial fusion (MNF-1, MNF-2, and OPA1), inhibited mitochondrial fission (Fis-1 and Drp-1), as well as increased mitophagy (autophagy of mitochondria). In addition, elamipretide has been shown to attenuate neural oxidative stress (hydrogen peroxide, lipid peroxidation, and ROS), neuroinflammation (TNF, IL-6, COX-2, iNOS, NLRP3, cleaved caspase-1, IL-1β, and IL-18), and toxic protein accumulation (Aβ). Consequently, elamipretide could prevent neural apoptosis (cytochrome c, Bax, caspase 9, and caspase 3) and enhance neural pro-survival (Bcl2, BDNF, and TrkB) in neurodegeneration. These findings suggest that elamipretide may prevent the progressive development of neurodegenerative diseases via enhancing mitochondrial respiration, mitochondrial biogenesis, mitochondrial fusion, and neural pro-survival pathway, as well as inhibiting mitochondrial fission, oxidative stress, neuroinflammation, toxic protein accumulation, and neural apoptosis. Elamipretide or mitochondrially-targeted peptide might be a targeted agent to attenuate neurodegenerative progression. Frontiers Media S.A. 2022-01-17 /pmc/articles/PMC8801496/ /pubmed/35111001 http://dx.doi.org/10.3389/fnint.2021.747901 Text en Copyright © 2022 Nhu, Xiao, Liu, Kumar, Cui and Lee. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Integrative Neuroscience Nhu, Nguyen Thanh Xiao, Shu-Yun Liu, Yijie Kumar, V. Bharath Cui, Zhen-Yang Lee, Shin-Da Neuroprotective Effects of a Small Mitochondrially-Targeted Tetrapeptide Elamipretide in Neurodegeneration |
title | Neuroprotective Effects of a Small Mitochondrially-Targeted Tetrapeptide Elamipretide in Neurodegeneration |
title_full | Neuroprotective Effects of a Small Mitochondrially-Targeted Tetrapeptide Elamipretide in Neurodegeneration |
title_fullStr | Neuroprotective Effects of a Small Mitochondrially-Targeted Tetrapeptide Elamipretide in Neurodegeneration |
title_full_unstemmed | Neuroprotective Effects of a Small Mitochondrially-Targeted Tetrapeptide Elamipretide in Neurodegeneration |
title_short | Neuroprotective Effects of a Small Mitochondrially-Targeted Tetrapeptide Elamipretide in Neurodegeneration |
title_sort | neuroprotective effects of a small mitochondrially-targeted tetrapeptide elamipretide in neurodegeneration |
topic | Integrative Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801496/ https://www.ncbi.nlm.nih.gov/pubmed/35111001 http://dx.doi.org/10.3389/fnint.2021.747901 |
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