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Abstract
Discussion Forum (0)
Microtubule acetylation rescues capsaicin-induced neurite degeneration and may predict fiber regeneration
Poster No: 1039
Presenter: Daniele Cartelli
Institution: Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
Introduction: Sensory nerve endings degenerate as the consequence of different insults, like immune-mediated or metabolic diseases and chemotherapy, but they also show unique regenerative capability. The mechanisms behind these processes might differ in the various disorders, and the reason why some patients show higher spontaneous nerve fiber regeneration is unknown.
Methods: To better understand the mechanisms underlying sensory neurons degeneration and regrowth, we used the experimental capsaicin treatment, a model that can be easily applied to cell cultures and transferred to human beings. Capsaicin, an agonist of transient receptor potential vanilloid type 1 channel, induces a fast degeneration of peripheral sensory nerves, with dynamic reorganization of microtubules and formation of axonal swellings reminiscent of intracellular trafficking block. We selected 10 small fiber neuropathy patients whose follow-up (range 3-6 months) distal leg skin biopsy showed either recovery or worsening of intraepidermal nerve fiber density (IENFD) compared to baseline biopsy. Moreover, we challenged differentiated F11 cells with capsaicin and performed a broader investigation of cell morphology and 3D architecture of microtubule network. F11 cells were also exposed to ricolinostat (ACY-1215), a first-in-line inhibitor of HDAC6 known to increase microtubule acetylation.
Results: Baseline biopsies of patients showing improved follow-up IENFD revealed a 2-fold increase of acetylated-positive/PGP9.5-negative fibers compared to those with worsened IENFD. In F11 cells, capsaicin treatment caused reorganization of the microtubule system, shortening of neurites and axonal swellings, whereas ricolinostat-induced microtubule acetylation reduced axon varicosities and promoted neurites elongation.
Conclusions: Our findings suggest that modulation of microtubule acetylation can be neuroprotective and acetylated-positive/PGP9.5-negative rate is a valuable proxy of nerve ending regeneration in small fiber neuropathy patients. These data are under validation in murine sensory neurons and capsaicin-treated healthy volunteers.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: Axon regeneration, Micotubule acetylation, Capsaicin, Small fiber neuropathy, HDAC6-inhibitor
Poster No: 1039
Presenter: Daniele Cartelli
Institution: Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
Introduction: Sensory nerve endings degenerate as the consequence of different insults, like immune-mediated or metabolic diseases and chemotherapy, but they also show unique regenerative capability. The mechanisms behind these processes might differ in the various disorders, and the reason why some patients show higher spontaneous nerve fiber regeneration is unknown.
Methods: To better understand the mechanisms underlying sensory neurons degeneration and regrowth, we used the experimental capsaicin treatment, a model that can be easily applied to cell cultures and transferred to human beings. Capsaicin, an agonist of transient receptor potential vanilloid type 1 channel, induces a fast degeneration of peripheral sensory nerves, with dynamic reorganization of microtubules and formation of axonal swellings reminiscent of intracellular trafficking block. We selected 10 small fiber neuropathy patients whose follow-up (range 3-6 months) distal leg skin biopsy showed either recovery or worsening of intraepidermal nerve fiber density (IENFD) compared to baseline biopsy. Moreover, we challenged differentiated F11 cells with capsaicin and performed a broader investigation of cell morphology and 3D architecture of microtubule network. F11 cells were also exposed to ricolinostat (ACY-1215), a first-in-line inhibitor of HDAC6 known to increase microtubule acetylation.
Results: Baseline biopsies of patients showing improved follow-up IENFD revealed a 2-fold increase of acetylated-positive/PGP9.5-negative fibers compared to those with worsened IENFD. In F11 cells, capsaicin treatment caused reorganization of the microtubule system, shortening of neurites and axonal swellings, whereas ricolinostat-induced microtubule acetylation reduced axon varicosities and promoted neurites elongation.
Conclusions: Our findings suggest that modulation of microtubule acetylation can be neuroprotective and acetylated-positive/PGP9.5-negative rate is a valuable proxy of nerve ending regeneration in small fiber neuropathy patients. These data are under validation in murine sensory neurons and capsaicin-treated healthy volunteers.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: Axon regeneration, Micotubule acetylation, Capsaicin, Small fiber neuropathy, HDAC6-inhibitor
Microtubule acetylation rescues capsaicin-induced neurite degeneration and may predict fiber regeneration
Poster No: 1039
Presenter: Daniele Cartelli
Institution: Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
Introduction: Sensory nerve endings degenerate as the consequence of different insults, like immune-mediated or metabolic diseases and chemotherapy, but they also show unique regenerative capability. The mechanisms behind these processes might differ in the various disorders, and the reason why some patients show higher spontaneous nerve fiber regeneration is unknown.
Methods: To better understand the mechanisms underlying sensory neurons degeneration and regrowth, we used the experimental capsaicin treatment, a model that can be easily applied to cell cultures and transferred to human beings. Capsaicin, an agonist of transient receptor potential vanilloid type 1 channel, induces a fast degeneration of peripheral sensory nerves, with dynamic reorganization of microtubules and formation of axonal swellings reminiscent of intracellular trafficking block. We selected 10 small fiber neuropathy patients whose follow-up (range 3-6 months) distal leg skin biopsy showed either recovery or worsening of intraepidermal nerve fiber density (IENFD) compared to baseline biopsy. Moreover, we challenged differentiated F11 cells with capsaicin and performed a broader investigation of cell morphology and 3D architecture of microtubule network. F11 cells were also exposed to ricolinostat (ACY-1215), a first-in-line inhibitor of HDAC6 known to increase microtubule acetylation.
Results: Baseline biopsies of patients showing improved follow-up IENFD revealed a 2-fold increase of acetylated-positive/PGP9.5-negative fibers compared to those with worsened IENFD. In F11 cells, capsaicin treatment caused reorganization of the microtubule system, shortening of neurites and axonal swellings, whereas ricolinostat-induced microtubule acetylation reduced axon varicosities and promoted neurites elongation.
Conclusions: Our findings suggest that modulation of microtubule acetylation can be neuroprotective and acetylated-positive/PGP9.5-negative rate is a valuable proxy of nerve ending regeneration in small fiber neuropathy patients. These data are under validation in murine sensory neurons and capsaicin-treated healthy volunteers.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: Axon regeneration, Micotubule acetylation, Capsaicin, Small fiber neuropathy, HDAC6-inhibitor
Poster No: 1039
Presenter: Daniele Cartelli
Institution: Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
Introduction: Sensory nerve endings degenerate as the consequence of different insults, like immune-mediated or metabolic diseases and chemotherapy, but they also show unique regenerative capability. The mechanisms behind these processes might differ in the various disorders, and the reason why some patients show higher spontaneous nerve fiber regeneration is unknown.
Methods: To better understand the mechanisms underlying sensory neurons degeneration and regrowth, we used the experimental capsaicin treatment, a model that can be easily applied to cell cultures and transferred to human beings. Capsaicin, an agonist of transient receptor potential vanilloid type 1 channel, induces a fast degeneration of peripheral sensory nerves, with dynamic reorganization of microtubules and formation of axonal swellings reminiscent of intracellular trafficking block. We selected 10 small fiber neuropathy patients whose follow-up (range 3-6 months) distal leg skin biopsy showed either recovery or worsening of intraepidermal nerve fiber density (IENFD) compared to baseline biopsy. Moreover, we challenged differentiated F11 cells with capsaicin and performed a broader investigation of cell morphology and 3D architecture of microtubule network. F11 cells were also exposed to ricolinostat (ACY-1215), a first-in-line inhibitor of HDAC6 known to increase microtubule acetylation.
Results: Baseline biopsies of patients showing improved follow-up IENFD revealed a 2-fold increase of acetylated-positive/PGP9.5-negative fibers compared to those with worsened IENFD. In F11 cells, capsaicin treatment caused reorganization of the microtubule system, shortening of neurites and axonal swellings, whereas ricolinostat-induced microtubule acetylation reduced axon varicosities and promoted neurites elongation.
Conclusions: Our findings suggest that modulation of microtubule acetylation can be neuroprotective and acetylated-positive/PGP9.5-negative rate is a valuable proxy of nerve ending regeneration in small fiber neuropathy patients. These data are under validation in murine sensory neurons and capsaicin-treated healthy volunteers.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: Axon regeneration, Micotubule acetylation, Capsaicin, Small fiber neuropathy, HDAC6-inhibitor
Microtubule acetylation rescues capsaicin-induced neurite degeneration and may predict fiber regeneration
Daniele Cartelli
Abstract
Discussion Forum (0)
Microtubule acetylation rescues capsaicin-induced neurite degeneration and may predict fiber regeneration
Poster No: 1039
Presenter: Daniele Cartelli
Institution: Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
Introduction: Sensory nerve endings degenerate as the consequence of different insults, like immune-mediated or metabolic diseases and chemotherapy, but they also show unique regenerative capability. The mechanisms behind these processes might differ in the various disorders, and the reason why some patients show higher spontaneous nerve fiber regeneration is unknown.
Methods: To better understand the mechanisms underlying sensory neurons degeneration and regrowth, we used the experimental capsaicin treatment, a model that can be easily applied to cell cultures and transferred to human beings. Capsaicin, an agonist of transient receptor potential vanilloid type 1 channel, induces a fast degeneration of peripheral sensory nerves, with dynamic reorganization of microtubules and formation of axonal swellings reminiscent of intracellular trafficking block. We selected 10 small fiber neuropathy patients whose follow-up (range 3-6 months) distal leg skin biopsy showed either recovery or worsening of intraepidermal nerve fiber density (IENFD) compared to baseline biopsy. Moreover, we challenged differentiated F11 cells with capsaicin and performed a broader investigation of cell morphology and 3D architecture of microtubule network. F11 cells were also exposed to ricolinostat (ACY-1215), a first-in-line inhibitor of HDAC6 known to increase microtubule acetylation.
Results: Baseline biopsies of patients showing improved follow-up IENFD revealed a 2-fold increase of acetylated-positive/PGP9.5-negative fibers compared to those with worsened IENFD. In F11 cells, capsaicin treatment caused reorganization of the microtubule system, shortening of neurites and axonal swellings, whereas ricolinostat-induced microtubule acetylation reduced axon varicosities and promoted neurites elongation.
Conclusions: Our findings suggest that modulation of microtubule acetylation can be neuroprotective and acetylated-positive/PGP9.5-negative rate is a valuable proxy of nerve ending regeneration in small fiber neuropathy patients. These data are under validation in murine sensory neurons and capsaicin-treated healthy volunteers.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: Axon regeneration, Micotubule acetylation, Capsaicin, Small fiber neuropathy, HDAC6-inhibitor
Poster No: 1039
Presenter: Daniele Cartelli
Institution: Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
Introduction: Sensory nerve endings degenerate as the consequence of different insults, like immune-mediated or metabolic diseases and chemotherapy, but they also show unique regenerative capability. The mechanisms behind these processes might differ in the various disorders, and the reason why some patients show higher spontaneous nerve fiber regeneration is unknown.
Methods: To better understand the mechanisms underlying sensory neurons degeneration and regrowth, we used the experimental capsaicin treatment, a model that can be easily applied to cell cultures and transferred to human beings. Capsaicin, an agonist of transient receptor potential vanilloid type 1 channel, induces a fast degeneration of peripheral sensory nerves, with dynamic reorganization of microtubules and formation of axonal swellings reminiscent of intracellular trafficking block. We selected 10 small fiber neuropathy patients whose follow-up (range 3-6 months) distal leg skin biopsy showed either recovery or worsening of intraepidermal nerve fiber density (IENFD) compared to baseline biopsy. Moreover, we challenged differentiated F11 cells with capsaicin and performed a broader investigation of cell morphology and 3D architecture of microtubule network. F11 cells were also exposed to ricolinostat (ACY-1215), a first-in-line inhibitor of HDAC6 known to increase microtubule acetylation.
Results: Baseline biopsies of patients showing improved follow-up IENFD revealed a 2-fold increase of acetylated-positive/PGP9.5-negative fibers compared to those with worsened IENFD. In F11 cells, capsaicin treatment caused reorganization of the microtubule system, shortening of neurites and axonal swellings, whereas ricolinostat-induced microtubule acetylation reduced axon varicosities and promoted neurites elongation.
Conclusions: Our findings suggest that modulation of microtubule acetylation can be neuroprotective and acetylated-positive/PGP9.5-negative rate is a valuable proxy of nerve ending regeneration in small fiber neuropathy patients. These data are under validation in murine sensory neurons and capsaicin-treated healthy volunteers.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: Axon regeneration, Micotubule acetylation, Capsaicin, Small fiber neuropathy, HDAC6-inhibitor
Microtubule acetylation rescues capsaicin-induced neurite degeneration and may predict fiber regeneration
Poster No: 1039
Presenter: Daniele Cartelli
Institution: Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
Introduction: Sensory nerve endings degenerate as the consequence of different insults, like immune-mediated or metabolic diseases and chemotherapy, but they also show unique regenerative capability. The mechanisms behind these processes might differ in the various disorders, and the reason why some patients show higher spontaneous nerve fiber regeneration is unknown.
Methods: To better understand the mechanisms underlying sensory neurons degeneration and regrowth, we used the experimental capsaicin treatment, a model that can be easily applied to cell cultures and transferred to human beings. Capsaicin, an agonist of transient receptor potential vanilloid type 1 channel, induces a fast degeneration of peripheral sensory nerves, with dynamic reorganization of microtubules and formation of axonal swellings reminiscent of intracellular trafficking block. We selected 10 small fiber neuropathy patients whose follow-up (range 3-6 months) distal leg skin biopsy showed either recovery or worsening of intraepidermal nerve fiber density (IENFD) compared to baseline biopsy. Moreover, we challenged differentiated F11 cells with capsaicin and performed a broader investigation of cell morphology and 3D architecture of microtubule network. F11 cells were also exposed to ricolinostat (ACY-1215), a first-in-line inhibitor of HDAC6 known to increase microtubule acetylation.
Results: Baseline biopsies of patients showing improved follow-up IENFD revealed a 2-fold increase of acetylated-positive/PGP9.5-negative fibers compared to those with worsened IENFD. In F11 cells, capsaicin treatment caused reorganization of the microtubule system, shortening of neurites and axonal swellings, whereas ricolinostat-induced microtubule acetylation reduced axon varicosities and promoted neurites elongation.
Conclusions: Our findings suggest that modulation of microtubule acetylation can be neuroprotective and acetylated-positive/PGP9.5-negative rate is a valuable proxy of nerve ending regeneration in small fiber neuropathy patients. These data are under validation in murine sensory neurons and capsaicin-treated healthy volunteers.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: Axon regeneration, Micotubule acetylation, Capsaicin, Small fiber neuropathy, HDAC6-inhibitor
Poster No: 1039
Presenter: Daniele Cartelli
Institution: Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
Introduction: Sensory nerve endings degenerate as the consequence of different insults, like immune-mediated or metabolic diseases and chemotherapy, but they also show unique regenerative capability. The mechanisms behind these processes might differ in the various disorders, and the reason why some patients show higher spontaneous nerve fiber regeneration is unknown.
Methods: To better understand the mechanisms underlying sensory neurons degeneration and regrowth, we used the experimental capsaicin treatment, a model that can be easily applied to cell cultures and transferred to human beings. Capsaicin, an agonist of transient receptor potential vanilloid type 1 channel, induces a fast degeneration of peripheral sensory nerves, with dynamic reorganization of microtubules and formation of axonal swellings reminiscent of intracellular trafficking block. We selected 10 small fiber neuropathy patients whose follow-up (range 3-6 months) distal leg skin biopsy showed either recovery or worsening of intraepidermal nerve fiber density (IENFD) compared to baseline biopsy. Moreover, we challenged differentiated F11 cells with capsaicin and performed a broader investigation of cell morphology and 3D architecture of microtubule network. F11 cells were also exposed to ricolinostat (ACY-1215), a first-in-line inhibitor of HDAC6 known to increase microtubule acetylation.
Results: Baseline biopsies of patients showing improved follow-up IENFD revealed a 2-fold increase of acetylated-positive/PGP9.5-negative fibers compared to those with worsened IENFD. In F11 cells, capsaicin treatment caused reorganization of the microtubule system, shortening of neurites and axonal swellings, whereas ricolinostat-induced microtubule acetylation reduced axon varicosities and promoted neurites elongation.
Conclusions: Our findings suggest that modulation of microtubule acetylation can be neuroprotective and acetylated-positive/PGP9.5-negative rate is a valuable proxy of nerve ending regeneration in small fiber neuropathy patients. These data are under validation in murine sensory neurons and capsaicin-treated healthy volunteers.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: Axon regeneration, Micotubule acetylation, Capsaicin, Small fiber neuropathy, HDAC6-inhibitor
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