dc.contributor.author | Carmona Abellán, Mar | |
dc.contributor.author | Gabilondo Cuellar, Iñigo | |
dc.contributor.author | Murueta-Goyena Larrañaga, Ane | |
dc.contributor.author | Khurana, Vikhram | |
dc.contributor.author | Tijero Merino, Beatriz | |
dc.contributor.author | Luquín, María Rosario | |
dc.contributor.author | Acera, Marian | |
dc.contributor.author | Del Pino Sáez, Rocío | |
dc.contributor.author | Gardeazabal García, Jesús | |
dc.contributor.author | Martínez-Valbuena, Iván | |
dc.contributor.author | Sánchez-Pernaute, Rosario | |
dc.contributor.author | Gómez Esteban, Juan Carlos | |
dc.date.accessioned | 2024-01-30T18:18:55Z | |
dc.date.available | 2024-01-30T18:18:55Z | |
dc.date.issued | 2019-06-05 | |
dc.identifier.citation | Parkinsonism & Related Disorders 65 : 139-145 (2019) | es_ES |
dc.identifier.issn | 1353-8020 | |
dc.identifier.uri | http://hdl.handle.net/10810/64481 | |
dc.description.abstract | 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. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | parkinson's disease | es_ES |
dc.subject | alpha-synuclein | es_ES |
dc.subject | E46K mutation | es_ES |
dc.subject | autonomic | es_ES |
dc.subject | skin biopsy | es_ES |
dc.title | Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K- SNCA mutation carriers | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2019 Elsevier under CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) | es_ES |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S1353802019302597 | es_ES |
dc.identifier.doi | 10.1016/j.parkreldis.2019.05.038 | |
dc.departamentoes | Neurociencias | es_ES |
dc.departamentoeu | Neurozientziak | es_ES |