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Journal article
Axonal Degeneration Is Mediated by the Mitochondrial Permeability Transition Pore
The Journal of neuroscience, v 41(48), pp 10031-10032
01 Dec 2021
Abstract
Axonal degeneration is an active process that has been associated with neurodegenerative conditions triggered by mechanical, metabolic, infectious, toxic, hereditary and inflammatory stimuli. This degenerative process can cause permanent loss of function, so it represents a focus for neuroprotective strategies. Several signaling pathways are implicated in axonal degeneration, but identification of an integrative mechanism for this self-destructive process has remained elusive. Here, we show that rapid axonal degeneration triggered by distinct mechanical and toxic insults is dependent on the activation of the mitochondrial permeability transition pore (mPTP). Both pharmacological and genetic targeting of cyclophilin D, a functional component of the mPTP, protects severed axons and vincristine-treated neurons from axonal degeneration in ex vivo and in vitro mouse and rat model systems. These effects were observed in axons from both the peripheral and central nervous system. Our results suggest that the mPTP is a key effector of axonal degeneration, upon which several independent signaling pathways converge. Since axonal and synapse degeneration are increasingly considered early pathological events in neurodegeneration, our work identifies a potential target for therapeutic intervention in a wide variety of conditions that lead to loss of axons and subsequent functional impairment.
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191 citations in Scopus
Details
- Title
- Axonal Degeneration Is Mediated by the Mitochondrial Permeability Transition Pore
- Creators
- Sebastian A. Barrientos - Pontifical Catholic University of ChileNicolas W. Martinez - Pontifical Catholic University of ChileSoonmoon Yoo - Alfred I. duPont Hospital for ChildrenJuan S. Jara - Pontifical Catholic University of ChileSebastian Zamorano - University of ChileClaudio Hetz - University of ChileJeffery L. Twiss - Drexel UniversityJaime Alvarez - Pontifical Catholic University of ChileFelipe A. Court - Pontifical Catholic University of Chile
- Publication Details
- The Journal of neuroscience, v 41(48), pp 10031-10032
- Publisher
- Soc Neuroscience
- Number of pages
- 2
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000726713400005
- Scopus ID
- 2-s2.0-78751565419
- Other Identifier
- 991021892106904721
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Neurosciences