Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K- SNCA mutation carriers

Background and objective: In 2004 we described the E46K mutation in alpha-synuclein gene (E46K-SNCA), a rare point mutation causing an aggressive Lewy body disease with early prominent non-motor features and small fiber denervation of myocardium. Considering the potential interest of the skin as a t...

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Autores: Carmona Abellán, Mar, Gabilondo Cuellar, Iñigo, Murueta-Goyena Larrañaga, Ane, Khurana, Vikhram, Tijero Merino, Beatriz, Luquín, María Rosario, Acera, Marian, Del Pino Sáez, Rocío, Gardeazabal García, Jesús, Martínez-Valbuena, Iván, Sánchez Pernaute, Rosario, Gómez Esteban, Juan Carlos
Tipo de documento: artigo
Data de publicação:2019
País:España
Recursos:Universidad del País Vasco
Repositório:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/64481
Acesso em linha:http://hdl.handle.net/10810/64481
Access Level:Acceso aberto
Palavra-chave:parkinson's disease
alpha-synuclein
E46K mutation
autonomic
skin biopsy
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spelling Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K- SNCA mutation carriersCarmona Abellán, MarGabilondo Cuellar, IñigoMurueta-Goyena Larrañaga, AneKhurana, VikhramTijero Merino, BeatrizLuquín, María RosarioAcera, MarianDel Pino Sáez, RocíoGardeazabal García, JesúsMartínez-Valbuena, IvánSánchez Pernaute, RosarioGómez Esteban, Juan Carlosparkinson's diseasealpha-synucleinE46K mutationautonomicskin biopsyBackground and objective: In 2004 we described the E46K mutation in alpha-synuclein gene (E46K-SNCA), a rare point mutation causing an aggressive Lewy body disease with early prominent non-motor features and small fiber denervation of myocardium. Considering the potential interest of the skin as a target for the development of biomarkers in Parkinson's Disease (PD), in this work we aimed to evaluate structural and functional integrity of small autonomic nerve fibers and phosphorylated alpha-synuclein (p-synuclein) deposition in the skin of E46K- SNCA carriers as compared to those observed in parkin gene mutation (PARK2) carriers and healthy controls. Patients and methods: We studied 7 E46K-SNCA carriers (3 dementia with Lewy bodies, 2 pure autonomic failure, 1 PD and 1 asymptomatic), 2 PARK2 carriers and 2 healthy controls to quantify intraepidermal nerve fiber density and p-synuclein deposition with cervical skin punch biopsies (immunohistochemistry against anti PGP9.5/UCHL-1, TH and p-synuclein) and sudomotor function with electrochemical skin conductance (ESC) (SudoScan). Results: All E46K-SNCA carriers had moderate to severe p-synuclein deposits and small fiber neurodegeneration in different epidermal and dermal structures including nerve fascicles and glands, especially in carriers with Pure Autonomic Failure, while p-synuclein aggregates where absent in healthy controls and in one of two PARK2 carriers. The severity of the latter skin abnormalities in E46K-SNCA were correlated with sudomotor dysfunction (lower ESC) in hands (p = 0.035). Interpretation: These results together with our previous findings support the relevance of E46K-SNCA mutation as a suitable model to study small fiber neuropathy in Lewy body diseases.Elsevier202420242019info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/64481reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.sciencedirect.com/science/article/pii/S1353802019302597info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/3.0/es/© 2019 Elsevier under CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)oai:addi.ehu.eus:10810/644812026-06-18T09:23:17Z
dc.title.none.fl_str_mv Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K- SNCA mutation carriers
title Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K- SNCA mutation carriers
spellingShingle Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K- SNCA mutation carriers
Carmona Abellán, Mar
parkinson's disease
alpha-synuclein
E46K mutation
autonomic
skin biopsy
title_short Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K- SNCA mutation carriers
title_full Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K- SNCA mutation carriers
title_fullStr Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K- SNCA mutation carriers
title_full_unstemmed Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K- SNCA mutation carriers
title_sort Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K- SNCA mutation carriers
dc.creator.none.fl_str_mv Carmona Abellán, Mar
Gabilondo Cuellar, Iñigo
Murueta-Goyena Larrañaga, Ane
Khurana, Vikhram
Tijero Merino, Beatriz
Luquín, María Rosario
Acera, Marian
Del Pino Sáez, Rocío
Gardeazabal García, Jesús
Martínez-Valbuena, Iván
Sánchez Pernaute, Rosario
Gómez Esteban, Juan Carlos
author Carmona Abellán, Mar
author_facet Carmona Abellán, Mar
Gabilondo Cuellar, Iñigo
Murueta-Goyena Larrañaga, Ane
Khurana, Vikhram
Tijero Merino, Beatriz
Luquín, María Rosario
Acera, Marian
Del Pino Sáez, Rocío
Gardeazabal García, Jesús
Martínez-Valbuena, Iván
Sánchez Pernaute, Rosario
Gómez Esteban, Juan Carlos
author_role author
author2 Gabilondo Cuellar, Iñigo
Murueta-Goyena Larrañaga, Ane
Khurana, Vikhram
Tijero Merino, Beatriz
Luquín, María Rosario
Acera, Marian
Del Pino Sáez, Rocío
Gardeazabal García, Jesús
Martínez-Valbuena, Iván
Sánchez Pernaute, Rosario
Gómez Esteban, Juan Carlos
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv parkinson's disease
alpha-synuclein
E46K mutation
autonomic
skin biopsy
topic parkinson's disease
alpha-synuclein
E46K mutation
autonomic
skin biopsy
description Background and objective: In 2004 we described the E46K mutation in alpha-synuclein gene (E46K-SNCA), a rare point mutation causing an aggressive Lewy body disease with early prominent non-motor features and small fiber denervation of myocardium. Considering the potential interest of the skin as a target for the development of biomarkers in Parkinson's Disease (PD), in this work we aimed to evaluate structural and functional integrity of small autonomic nerve fibers and phosphorylated alpha-synuclein (p-synuclein) deposition in the skin of E46K- SNCA carriers as compared to those observed in parkin gene mutation (PARK2) carriers and healthy controls. Patients and methods: We studied 7 E46K-SNCA carriers (3 dementia with Lewy bodies, 2 pure autonomic failure, 1 PD and 1 asymptomatic), 2 PARK2 carriers and 2 healthy controls to quantify intraepidermal nerve fiber density and p-synuclein deposition with cervical skin punch biopsies (immunohistochemistry against anti PGP9.5/UCHL-1, TH and p-synuclein) and sudomotor function with electrochemical skin conductance (ESC) (SudoScan). Results: All E46K-SNCA carriers had moderate to severe p-synuclein deposits and small fiber neurodegeneration in different epidermal and dermal structures including nerve fascicles and glands, especially in carriers with Pure Autonomic Failure, while p-synuclein aggregates where absent in healthy controls and in one of two PARK2 carriers. The severity of the latter skin abnormalities in E46K-SNCA were correlated with sudomotor dysfunction (lower ESC) in hands (p = 0.035). Interpretation: These results together with our previous findings support the relevance of E46K-SNCA mutation as a suitable model to study small fiber neuropathy in Lewy body diseases.
publishDate 2019
dc.date.none.fl_str_mv 2019
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/64481
url http://hdl.handle.net/10810/64481
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.sciencedirect.com/science/article/pii/S1353802019302597
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
© 2019 Elsevier under CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/es/
© 2019 Elsevier under CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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