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Upregulation of Heat-Shock Protein (hsp)-27 in a Patient with Heterozygous SPG11 c.1951C>T and SYNJ1 c.2614G>T Mutations Causing Clinical Spastic Paraplegia

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dc.contributor.authorGarcía Carmona, Juan Antonio
dc.contributor.authorAmores Iniesta, Joaquín
dc.contributor.authorSoler Usero, José
dc.contributor.authorCerdán Sánchez, María
dc.contributor.authorNavarro Zaragoza, Javier
dc.contributor.authorLópez López, María
dc.contributor.authorSoria Torrecillas, Juan José
dc.contributor.authorBallesteros Arenas, Ainhoa
dc.contributor.authorPérez Vicente, José Antonio
dc.contributor.authorAlmela Rojo, Pilar
dc.contributor.departmentFarmacología
dc.date.accessioned2026-03-27T11:46:04Z
dc.date.available2026-03-27T11:46:04Z
dc.date.issued2023-06-23
dc.description.abstractWe report a 49-year-old patient suffering from spastic paraplegia with a novel heterozygous mutation and analyzed the levels of heat shock proteins (hsp)-27, dopamine (DA), and its metabolites in their cerebrospinal fluid (CSF). The hsp27 protein concentration in the patient’s CSF was assayed by an ELISA kit, while DA levels and its metabolites in the CSF, 3,4-dihydroxyphenylacetic acid (DOPAC), Cys-DA, and Cys-DOPA were measured by HPLC. Whole exome sequencing demonstrated SPG-11 c.1951C>T and novel SYNJ1 c.2614G>T mutations, both heterozygous recessive. The patient’s DA and DOPAC levels in their CSF were significantly decreased (53.0 6.92 and 473.3 72.19, p < 0.05, respectively) while no differences were found in their Cys-DA. Nonetheless, Cys-DA/DOPAC ratio (0.213 0.024, p < 0.05) and hsp27 levels (1073.0 136.4, p < 0.05) were significantly higher. To the best of our knowledge, the c.2614G>T SYNJ1 mutation has not been previously reported. Our patient does not produce fully functional spatacsin and synaptojanin-1 proteins. In this line, our results showed decreased DA and DOPAC levels in the patient’s CSF, indicating loss of DAergic neurons. Many factors have been described as being responsible for the increased cys-DA/DOPAC ratio, such as MAO inhibition and decreased antioxidant activity in DAergic neurons which would increase catecholquinones and consequently cysteinyl-catechols. In conclusion, haploinsufficiency of spatacsin and synaptojanin-1 proteins might be the underlying cause of neurodegeneration produced by protein trafficking defects, DA vesicle trafficking/recycling processes, autophagy dysfunction, and cell death leading to hsp27 upregulation as a cellular mechanism of protection and/or to balance impaired protein trafficking.
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dc.identifier.citationGarcía-Carmona, J.A.; Amores-Iniesta, J.; Soler-Usero, J.; Cerdán-Sánchez, M.; Navarro-Zaragoza, J.; López-López, M.; Soria-Torrecillas, J.J.; Ballesteros-Arenas, A.; Pérez-Vicente, J.A.; Almela, P. Upregulation of Heat-Shock Protein (hsp)-27 in a Patient with Heterozygous SPG11 c.1951C>T and SYNJ1 c.2614G>T Mutations Causing Clinical Spastic Paraplegia. Genes 2023, 14, 1320. https://doi.org/10.3390/ genes14071320
dc.identifier.doidoi.org/10.3390/genes14071320
dc.identifier.issn2073-4425
dc.identifier.urihttp://hdl.handle.net/10201/223661
dc.languageeng
dc.relationThis study was supported by the Servicio Murciano de Salud, (Spain); the Spanish Ministry of Science ref: SAF/FEDER2017-83855-R and ref: PID2020-103611; and the Seneca Foundation: Science and Technology Agency of the Region of Murcia (Spain) ref: 20847/PI/18.
dc.relation.publisherversionhttps://www.mdpi.com/2073-4425/14/7/1320
dc.rightsAttribution 4.0 International
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectSpatacsin
dc.subjectSynaptojanin
dc.subjectHeat-shock protein 27
dc.subjectDopamine oxidation
dc.subjectSpastic paraplegia
dc.subject.odsObjetivo 3: Salud
dc.titleUpregulation of Heat-Shock Protein (hsp)-27 in a Patient with Heterozygous SPG11 c.1951C>T and SYNJ1 c.2614G>T Mutations Causing Clinical Spastic Paraplegia
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublicationes
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relation.isAuthorOfPublication91a9c0cf-0115-4c34-9b53-72a417c2d883
relation.isAuthorOfPublication5028b798-617b-4311-8389-11b8f71ac210
relation.isAuthorOfPublication.latestForDiscoveryed1a6db8-9052-4cc4-977c-4e32e92bc6e4
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