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Fluocinolone Acetonide Enhances Anterograde Mitochondria Trafficking and Promotes Neuroprotection against Paclitaxel-Induced Peripheral Neuropathy

[Image: see text] Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) is a debilitating health condition which is a result of degeneration of peripheral nerves found in extremities. Currently, there are no established treatment methods that can prevent or protect from PIPN. Fluocinolone acetonide...

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Autores principales: Tiwari, Arjun Prasad, Tristan, Lee Ji Chao, Albin, Bayne, Yang, In Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10251481/
https://www.ncbi.nlm.nih.gov/pubmed/37167105
http://dx.doi.org/10.1021/acschemneuro.3c00218
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author Tiwari, Arjun Prasad
Tristan, Lee Ji Chao
Albin, Bayne
Yang, In Hong
author_facet Tiwari, Arjun Prasad
Tristan, Lee Ji Chao
Albin, Bayne
Yang, In Hong
author_sort Tiwari, Arjun Prasad
collection PubMed
description [Image: see text] Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) is a debilitating health condition which is a result of degeneration of peripheral nerves found in extremities. Currently, there are no established treatment methods that can prevent or protect from PIPN. Fluocinolone acetonide (FA) has been recently identified as a potential candidate for protection from PIPN. However, the fundamental mechanism of action is still unknown. In this study, we showed that enhanced anterograde mitochondrial movement in dorsal root ganglion (DRG) cells has a major role in FA-mediated neuroprotection in PIPN. In this study, cells were treated with PTX or FA along with their combination followed by mitochondrial fluorescence staining. Somal (proximal) and axonal (distal) mitochondria were selectively stained using a microfluidic compartmentalized chamber with different MitoTrackers blue and red, respectively, which we termed, the two-color staining approach. Results revealed that axons were protected from degeneration by the PTX effect when treated along with FA. PTX exposure alone resulted in low mitochondrial mobility in DRG cells. However, cotreatment with PTX and FA showed significant enhancement of anterograde trafficking of somal (proximal) mitochondria to distal axons. Similarly, cotreatment with FA restored mitochondrial mobility significantly. Overall, this study affirms that increasing mitochondrial recruitment into the axon by cotreatment with FA can be a worthwhile strategy to protect or prevent PIPN. The proposed two-color staining approach can be extended to study trafficking for other neuron-specific subcellular organelles.
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spelling pubmed-102514812023-06-10 Fluocinolone Acetonide Enhances Anterograde Mitochondria Trafficking and Promotes Neuroprotection against Paclitaxel-Induced Peripheral Neuropathy Tiwari, Arjun Prasad Tristan, Lee Ji Chao Albin, Bayne Yang, In Hong ACS Chem Neurosci [Image: see text] Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) is a debilitating health condition which is a result of degeneration of peripheral nerves found in extremities. Currently, there are no established treatment methods that can prevent or protect from PIPN. Fluocinolone acetonide (FA) has been recently identified as a potential candidate for protection from PIPN. However, the fundamental mechanism of action is still unknown. In this study, we showed that enhanced anterograde mitochondrial movement in dorsal root ganglion (DRG) cells has a major role in FA-mediated neuroprotection in PIPN. In this study, cells were treated with PTX or FA along with their combination followed by mitochondrial fluorescence staining. Somal (proximal) and axonal (distal) mitochondria were selectively stained using a microfluidic compartmentalized chamber with different MitoTrackers blue and red, respectively, which we termed, the two-color staining approach. Results revealed that axons were protected from degeneration by the PTX effect when treated along with FA. PTX exposure alone resulted in low mitochondrial mobility in DRG cells. However, cotreatment with PTX and FA showed significant enhancement of anterograde trafficking of somal (proximal) mitochondria to distal axons. Similarly, cotreatment with FA restored mitochondrial mobility significantly. Overall, this study affirms that increasing mitochondrial recruitment into the axon by cotreatment with FA can be a worthwhile strategy to protect or prevent PIPN. The proposed two-color staining approach can be extended to study trafficking for other neuron-specific subcellular organelles. American Chemical Society 2023-05-11 /pmc/articles/PMC10251481/ /pubmed/37167105 http://dx.doi.org/10.1021/acschemneuro.3c00218 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Tiwari, Arjun Prasad
Tristan, Lee Ji Chao
Albin, Bayne
Yang, In Hong
Fluocinolone Acetonide Enhances Anterograde Mitochondria Trafficking and Promotes Neuroprotection against Paclitaxel-Induced Peripheral Neuropathy
title Fluocinolone Acetonide Enhances Anterograde Mitochondria Trafficking and Promotes Neuroprotection against Paclitaxel-Induced Peripheral Neuropathy
title_full Fluocinolone Acetonide Enhances Anterograde Mitochondria Trafficking and Promotes Neuroprotection against Paclitaxel-Induced Peripheral Neuropathy
title_fullStr Fluocinolone Acetonide Enhances Anterograde Mitochondria Trafficking and Promotes Neuroprotection against Paclitaxel-Induced Peripheral Neuropathy
title_full_unstemmed Fluocinolone Acetonide Enhances Anterograde Mitochondria Trafficking and Promotes Neuroprotection against Paclitaxel-Induced Peripheral Neuropathy
title_short Fluocinolone Acetonide Enhances Anterograde Mitochondria Trafficking and Promotes Neuroprotection against Paclitaxel-Induced Peripheral Neuropathy
title_sort fluocinolone acetonide enhances anterograde mitochondria trafficking and promotes neuroprotection against paclitaxel-induced peripheral neuropathy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10251481/
https://www.ncbi.nlm.nih.gov/pubmed/37167105
http://dx.doi.org/10.1021/acschemneuro.3c00218
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