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Janus-faced spatacsin (SPG11): involvement in neurodevelopment and multisystem neurodegeneration

Hereditary spastic paraplegia (HSP) is a heterogeneous group of rare motor neuron disorders characterized by progressive weakness and spasticity of the lower limbs. HSP type 11 (SPG11-HSP) is linked to pathogenic variants in the SPG11 gene and it represents the most frequent form of complex autosoma...

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Autores principales: Pozner, Tatyana, Regensburger, Martin, Engelhorn, Tobias, Winkler, Jürgen, Winner, Beate
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447516/
https://www.ncbi.nlm.nih.gov/pubmed/32355960
http://dx.doi.org/10.1093/brain/awaa099
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author Pozner, Tatyana
Regensburger, Martin
Engelhorn, Tobias
Winkler, Jürgen
Winner, Beate
author_facet Pozner, Tatyana
Regensburger, Martin
Engelhorn, Tobias
Winkler, Jürgen
Winner, Beate
author_sort Pozner, Tatyana
collection PubMed
description Hereditary spastic paraplegia (HSP) is a heterogeneous group of rare motor neuron disorders characterized by progressive weakness and spasticity of the lower limbs. HSP type 11 (SPG11-HSP) is linked to pathogenic variants in the SPG11 gene and it represents the most frequent form of complex autosomal recessive HSP. The majority of SPG11-HSP patients exhibit additional neurological symptoms such as cognitive decline, thin corpus callosum, and peripheral neuropathy. Yet, the mechanisms of SPG11-linked spectrum diseases are largely unknown. Recent findings indicate that spatacsin, the 280 kDa protein encoded by SPG11, may impact the autophagy-lysosomal machinery. In this update, we summarize the current knowledge of SPG11-HSP. In addition to clinical symptoms and differential diagnosis, our work aims to link the different clinical manifestations with the respective structural abnormalities and cellular in vitro phenotypes. Moreover, we describe the impact of localization and function of spatacsin in different neuronal systems. Ultimately, we propose a model in which spatacsin bridges between neurodevelopmental and neurodegenerative phenotypes of SPG11-linked disorders.
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spelling pubmed-74475162020-08-27 Janus-faced spatacsin (SPG11): involvement in neurodevelopment and multisystem neurodegeneration Pozner, Tatyana Regensburger, Martin Engelhorn, Tobias Winkler, Jürgen Winner, Beate Brain Update Hereditary spastic paraplegia (HSP) is a heterogeneous group of rare motor neuron disorders characterized by progressive weakness and spasticity of the lower limbs. HSP type 11 (SPG11-HSP) is linked to pathogenic variants in the SPG11 gene and it represents the most frequent form of complex autosomal recessive HSP. The majority of SPG11-HSP patients exhibit additional neurological symptoms such as cognitive decline, thin corpus callosum, and peripheral neuropathy. Yet, the mechanisms of SPG11-linked spectrum diseases are largely unknown. Recent findings indicate that spatacsin, the 280 kDa protein encoded by SPG11, may impact the autophagy-lysosomal machinery. In this update, we summarize the current knowledge of SPG11-HSP. In addition to clinical symptoms and differential diagnosis, our work aims to link the different clinical manifestations with the respective structural abnormalities and cellular in vitro phenotypes. Moreover, we describe the impact of localization and function of spatacsin in different neuronal systems. Ultimately, we propose a model in which spatacsin bridges between neurodevelopmental and neurodegenerative phenotypes of SPG11-linked disorders. Oxford University Press 2020-08 2020-05-01 /pmc/articles/PMC7447516/ /pubmed/32355960 http://dx.doi.org/10.1093/brain/awaa099 Text en © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Update
Pozner, Tatyana
Regensburger, Martin
Engelhorn, Tobias
Winkler, Jürgen
Winner, Beate
Janus-faced spatacsin (SPG11): involvement in neurodevelopment and multisystem neurodegeneration
title Janus-faced spatacsin (SPG11): involvement in neurodevelopment and multisystem neurodegeneration
title_full Janus-faced spatacsin (SPG11): involvement in neurodevelopment and multisystem neurodegeneration
title_fullStr Janus-faced spatacsin (SPG11): involvement in neurodevelopment and multisystem neurodegeneration
title_full_unstemmed Janus-faced spatacsin (SPG11): involvement in neurodevelopment and multisystem neurodegeneration
title_short Janus-faced spatacsin (SPG11): involvement in neurodevelopment and multisystem neurodegeneration
title_sort janus-faced spatacsin (spg11): involvement in neurodevelopment and multisystem neurodegeneration
topic Update
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447516/
https://www.ncbi.nlm.nih.gov/pubmed/32355960
http://dx.doi.org/10.1093/brain/awaa099
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