The childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) disease caused by AGTPBP1 gene mutations: the Purkinje cell degeneration mouse as an animal model for the study of this human disease

Recent reports have identified rare, biallelic damaging variants of the AGTPBP1 gene that cause a novel and documented human disease known as childhood-onset neurodegeneration with cerebellar atrophy (CONDCA), linking loss of function of the AGTPBP1 protein to human neurode generative diseases. COND...

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Detalles Bibliográficos
Autores: Baltanás, Fernando C., Berciano Blanco, María Teresa, Santos, Eugenio, Lafarga Coscojuela, Miguel Ángel|||0000-0003-3402-1152
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/22379
Acceso en línea:http://hdl.handle.net/10902/22379
Access Level:acceso abierto
Palabra clave:AGTPBP1
CCP1
CONDCA
Neurodegeneration
NNA1
Pcd
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spelling The childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) disease caused by AGTPBP1 gene mutations: the Purkinje cell degeneration mouse as an animal model for the study of this human diseaseBaltanás, Fernando C.Berciano Blanco, María TeresaSantos, EugenioLafarga Coscojuela, Miguel Ángel|||0000-0003-3402-1152AGTPBP1CCP1CONDCANeurodegenerationNNA1PcdRecent reports have identified rare, biallelic damaging variants of the AGTPBP1 gene that cause a novel and documented human disease known as childhood-onset neurodegeneration with cerebellar atrophy (CONDCA), linking loss of function of the AGTPBP1 protein to human neurode generative diseases. CONDCA patients exhibit progressive cognitive decline, ataxia, hypotonia or muscle weakness among other clinical features that may be fatal. Loss of AGTPBP1 in humans recapitulates the neurodegenerative course reported in a well-characterised murine animal model harbouring loss-of-function mutations in the AGTPBP1 gene. In particular, in the Purkinje cell degen eration (pcd) mouse model, mutations in AGTPBP1 lead to early cerebellar ataxia, which correlates with the massive loss of cerebellar Purkinje cells. In addition, neurodegeneration in the olfactory bulb, retina, thalamus and spinal cord were also reported. In addition to neurodegeneration, pcd mice show behavioural deficits such as cognitive decline. Here, we provide an overview of what is currently known about the structure and functional role of AGTPBP1 and discuss the various alterations in AGTPBP1 that cause neurodegeneration in the pcd mutant mouse and humans with CONDCA. The sequence of neuropathological events that occur in pcd mice and the mechanisms governing these neurodegenerative processes are also reported. Finally, we describe the therapeutic strategies that were applied in pcd mice and focus on the potential usefulness of pcd mice as a promising model for the development of new therapeutic strategies for clinical trials in humans, which may offer potential beneficial options for patients with AGTPBP1 mutation-related CONDCA.MDPI AGUniversidad de Cantabria20212021-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttp://hdl.handle.net/10902/22379Biomedicines 2021, 9(9), 1157reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/223792026-06-02T12:39:31Z
dc.title.none.fl_str_mv The childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) disease caused by AGTPBP1 gene mutations: the Purkinje cell degeneration mouse as an animal model for the study of this human disease
title The childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) disease caused by AGTPBP1 gene mutations: the Purkinje cell degeneration mouse as an animal model for the study of this human disease
spellingShingle The childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) disease caused by AGTPBP1 gene mutations: the Purkinje cell degeneration mouse as an animal model for the study of this human disease
Baltanás, Fernando C.
AGTPBP1
CCP1
CONDCA
Neurodegeneration
NNA1
Pcd
title_short The childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) disease caused by AGTPBP1 gene mutations: the Purkinje cell degeneration mouse as an animal model for the study of this human disease
title_full The childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) disease caused by AGTPBP1 gene mutations: the Purkinje cell degeneration mouse as an animal model for the study of this human disease
title_fullStr The childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) disease caused by AGTPBP1 gene mutations: the Purkinje cell degeneration mouse as an animal model for the study of this human disease
title_full_unstemmed The childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) disease caused by AGTPBP1 gene mutations: the Purkinje cell degeneration mouse as an animal model for the study of this human disease
title_sort The childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) disease caused by AGTPBP1 gene mutations: the Purkinje cell degeneration mouse as an animal model for the study of this human disease
dc.creator.none.fl_str_mv Baltanás, Fernando C.
Berciano Blanco, María Teresa
Santos, Eugenio
Lafarga Coscojuela, Miguel Ángel|||0000-0003-3402-1152
author Baltanás, Fernando C.
author_facet Baltanás, Fernando C.
Berciano Blanco, María Teresa
Santos, Eugenio
Lafarga Coscojuela, Miguel Ángel|||0000-0003-3402-1152
author_role author
author2 Berciano Blanco, María Teresa
Santos, Eugenio
Lafarga Coscojuela, Miguel Ángel|||0000-0003-3402-1152
author2_role author
author
author
dc.contributor.none.fl_str_mv Universidad de Cantabria
dc.subject.none.fl_str_mv AGTPBP1
CCP1
CONDCA
Neurodegeneration
NNA1
Pcd
topic AGTPBP1
CCP1
CONDCA
Neurodegeneration
NNA1
Pcd
description Recent reports have identified rare, biallelic damaging variants of the AGTPBP1 gene that cause a novel and documented human disease known as childhood-onset neurodegeneration with cerebellar atrophy (CONDCA), linking loss of function of the AGTPBP1 protein to human neurode generative diseases. CONDCA patients exhibit progressive cognitive decline, ataxia, hypotonia or muscle weakness among other clinical features that may be fatal. Loss of AGTPBP1 in humans recapitulates the neurodegenerative course reported in a well-characterised murine animal model harbouring loss-of-function mutations in the AGTPBP1 gene. In particular, in the Purkinje cell degen eration (pcd) mouse model, mutations in AGTPBP1 lead to early cerebellar ataxia, which correlates with the massive loss of cerebellar Purkinje cells. In addition, neurodegeneration in the olfactory bulb, retina, thalamus and spinal cord were also reported. In addition to neurodegeneration, pcd mice show behavioural deficits such as cognitive decline. Here, we provide an overview of what is currently known about the structure and functional role of AGTPBP1 and discuss the various alterations in AGTPBP1 that cause neurodegeneration in the pcd mutant mouse and humans with CONDCA. The sequence of neuropathological events that occur in pcd mice and the mechanisms governing these neurodegenerative processes are also reported. Finally, we describe the therapeutic strategies that were applied in pcd mice and focus on the potential usefulness of pcd mice as a promising model for the development of new therapeutic strategies for clinical trials in humans, which may offer potential beneficial options for patients with AGTPBP1 mutation-related CONDCA.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10902/22379
url http://hdl.handle.net/10902/22379
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI AG
publisher.none.fl_str_mv MDPI AG
dc.source.none.fl_str_mv Biomedicines 2021, 9(9), 1157
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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