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Retrograde Axonal Degeneration in Parkinson Disease

In spite of tremendous research efforts we have not yet achieved two of our principal therapeutic goals in the treatment of Parkinson’s disease (PD), to prevent its onward progression and to provide restoration of systems that have already been damaged by the time of diagnosis. There are many possib...

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Autores principales: Tagliaferro, Patricia, Burke, Robert E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927911/
https://www.ncbi.nlm.nih.gov/pubmed/27003783
http://dx.doi.org/10.3233/JPD-150769
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author Tagliaferro, Patricia
Burke, Robert E.
author_facet Tagliaferro, Patricia
Burke, Robert E.
author_sort Tagliaferro, Patricia
collection PubMed
description In spite of tremendous research efforts we have not yet achieved two of our principal therapeutic goals in the treatment of Parkinson’s disease (PD), to prevent its onward progression and to provide restoration of systems that have already been damaged by the time of diagnosis. There are many possible reasons for our inability to make progress. One possibility is that our efforts thus far may not have been directed towards the appropriate cellular compartments. Up until now research has been largely focused on the loss of neurons in the disease. Thus, neuroprotection approaches have been largely aimed at blocking mechanisms that lead to destruction of the neuronal cell body. Attempts to provide neurorestoration have been almost entirely focused on replacement of neurons. We herein review the evidence that the axonal component of diseased neuronal systems merit more of our attention. Evidence from imaging studies, from postmortem neurochemical studies, and from genetic animal models suggests that the axons of the dopaminergic system are involved predominantly and early in PD. Since the mechanisms of axonal destruction are distinct from those of neuron cell body degeneration, a focus on axonal neurobiology will offer new opportunities for preventing their degeneration. At present these mechanisms remain largely obscure. However, defining them is likely to offer new opportunities for neuroprotection. In relation to neurorestoration, while it has been classically believed that neurons of the adult central nervous system are incapable of new axon growth, recent evidence shows that this is not true for the dopaminergic projection. In conclusion, the neurobiology of axons is likely to offer many new approaches to protective and restorative therapeutics.
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spelling pubmed-49279112016-06-30 Retrograde Axonal Degeneration in Parkinson Disease Tagliaferro, Patricia Burke, Robert E. J Parkinsons Dis Review In spite of tremendous research efforts we have not yet achieved two of our principal therapeutic goals in the treatment of Parkinson’s disease (PD), to prevent its onward progression and to provide restoration of systems that have already been damaged by the time of diagnosis. There are many possible reasons for our inability to make progress. One possibility is that our efforts thus far may not have been directed towards the appropriate cellular compartments. Up until now research has been largely focused on the loss of neurons in the disease. Thus, neuroprotection approaches have been largely aimed at blocking mechanisms that lead to destruction of the neuronal cell body. Attempts to provide neurorestoration have been almost entirely focused on replacement of neurons. We herein review the evidence that the axonal component of diseased neuronal systems merit more of our attention. Evidence from imaging studies, from postmortem neurochemical studies, and from genetic animal models suggests that the axons of the dopaminergic system are involved predominantly and early in PD. Since the mechanisms of axonal destruction are distinct from those of neuron cell body degeneration, a focus on axonal neurobiology will offer new opportunities for preventing their degeneration. At present these mechanisms remain largely obscure. However, defining them is likely to offer new opportunities for neuroprotection. In relation to neurorestoration, while it has been classically believed that neurons of the adult central nervous system are incapable of new axon growth, recent evidence shows that this is not true for the dopaminergic projection. In conclusion, the neurobiology of axons is likely to offer many new approaches to protective and restorative therapeutics. IOS Press 2016-03-30 /pmc/articles/PMC4927911/ /pubmed/27003783 http://dx.doi.org/10.3233/JPD-150769 Text en IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Tagliaferro, Patricia
Burke, Robert E.
Retrograde Axonal Degeneration in Parkinson Disease
title Retrograde Axonal Degeneration in Parkinson Disease
title_full Retrograde Axonal Degeneration in Parkinson Disease
title_fullStr Retrograde Axonal Degeneration in Parkinson Disease
title_full_unstemmed Retrograde Axonal Degeneration in Parkinson Disease
title_short Retrograde Axonal Degeneration in Parkinson Disease
title_sort retrograde axonal degeneration in parkinson disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927911/
https://www.ncbi.nlm.nih.gov/pubmed/27003783
http://dx.doi.org/10.3233/JPD-150769
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