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Stathmin-2 loss leads to neurofilament-dependent axonal collapse driving motor and sensory denervation
Stathmin-2 loss leads to neurofilament-dependent axonal collapse driving motor and sensory denervation
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Length:
20 minutes
Released:
Dec 12, 2022
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2022.12.11.519794v1?rss=1
Authors: Lopez-Erauskin, J., Bravo-Hernandez, M., Presa, M., Baughn, M. W., Melamed, Z., Beccari, M. S., Agra de Almeida Quadros, A. R., Zuberi, A., Ling, K., Platoshyn, O., Nino-Jara, E., Ndayambaje, I. S., Arnold-Garcia, O., McAlonis-Downes, M., Cabrera, L., Artates, J. W., Ryan, J., Bennett, F., Jafar-nejad, P., Rigo, F., Marsala, M., Lutz, C. M., Cleveland, D. W., Lagier-Tourenne, C.
Abstract:
The human mRNA most affected by TDP-43 loss-of-function is transcribed from the STMN2 gene and encodes stathmin-2 (also known as SCG10), whose loss is a neurodegenerative disease hallmark. Here using multiple in vivo approaches, including transient antisense oligonucleotide (ASO)-mediated suppression, chronic shRNA-mediated depletion in aging mice, and germline deletion, we establish stathmin-2 to be essential for acquisition and maintenance of neurofilament-dependent structuring of axoplasm critical for maintaining diameter and conduction velocity of large-myelinated axons. Sustained stathmin-2 loss from an otherwise mature adult nervous system is demonstrated over a time course of eight months to initiate and drive motor neuron disease that includes 1) shrinkage in inter-neurofilament spacing that is required to produce a three-dimensional space filling array that defines axonal caliber, 2) collapse of mature axonal caliber with tearing of outer myelin layers, 3) reduced conduction velocity, 4) progressive motor and sensory deficits (including reduction of the pain transducing neuropeptide CGRP), and 5) muscle denervation. Demonstration that chronic stathmin-2 reduction is itself sufficient to trigger motor neuron disease reinforces restoration of stathmin-2 as an attractive therapeutic approach for TDP-43-dependent neurodegeneration, including the fatal adult motor neuron disease ALS.
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http://biorxiv.org/cgi/content/short/2022.12.11.519794v1?rss=1
Authors: Lopez-Erauskin, J., Bravo-Hernandez, M., Presa, M., Baughn, M. W., Melamed, Z., Beccari, M. S., Agra de Almeida Quadros, A. R., Zuberi, A., Ling, K., Platoshyn, O., Nino-Jara, E., Ndayambaje, I. S., Arnold-Garcia, O., McAlonis-Downes, M., Cabrera, L., Artates, J. W., Ryan, J., Bennett, F., Jafar-nejad, P., Rigo, F., Marsala, M., Lutz, C. M., Cleveland, D. W., Lagier-Tourenne, C.
Abstract:
The human mRNA most affected by TDP-43 loss-of-function is transcribed from the STMN2 gene and encodes stathmin-2 (also known as SCG10), whose loss is a neurodegenerative disease hallmark. Here using multiple in vivo approaches, including transient antisense oligonucleotide (ASO)-mediated suppression, chronic shRNA-mediated depletion in aging mice, and germline deletion, we establish stathmin-2 to be essential for acquisition and maintenance of neurofilament-dependent structuring of axoplasm critical for maintaining diameter and conduction velocity of large-myelinated axons. Sustained stathmin-2 loss from an otherwise mature adult nervous system is demonstrated over a time course of eight months to initiate and drive motor neuron disease that includes 1) shrinkage in inter-neurofilament spacing that is required to produce a three-dimensional space filling array that defines axonal caliber, 2) collapse of mature axonal caliber with tearing of outer myelin layers, 3) reduced conduction velocity, 4) progressive motor and sensory deficits (including reduction of the pain transducing neuropeptide CGRP), and 5) muscle denervation. Demonstration that chronic stathmin-2 reduction is itself sufficient to trigger motor neuron disease reinforces restoration of stathmin-2 as an attractive therapeutic approach for TDP-43-dependent neurodegeneration, including the fatal adult motor neuron disease ALS.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Dec 12, 2022
Format:
Podcast episode
Titles in the series (100)
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