{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:16:42Z","timestamp":1760149002394,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T00:00:00Z","timestamp":1687478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Servicio Murciano de Salud, (Spain)","award":["SAF\/FEDER2017-83855-R","PID2020-103611","20847\/PI\/18"],"award-info":[{"award-number":["SAF\/FEDER2017-83855-R","PID2020-103611","20847\/PI\/18"]}]},{"name":"Spanish Ministry of Science","award":["SAF\/FEDER2017-83855-R","PID2020-103611","20847\/PI\/18"],"award-info":[{"award-number":["SAF\/FEDER2017-83855-R","PID2020-103611","20847\/PI\/18"]}]},{"name":"Seneca Foundation: Science and Technology Agency of the Region of Murcia (Spain)","award":["SAF\/FEDER2017-83855-R","PID2020-103611","20847\/PI\/18"],"award-info":[{"award-number":["SAF\/FEDER2017-83855-R","PID2020-103611","20847\/PI\/18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>We 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\u2019s 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&gt;T and novel SYNJ1 c.2614G&gt;T mutations, both heterozygous recessive. The patient\u2019s DA and DOPAC levels in their CSF were significantly decreased (53.0 \u00b1 6.92 and 473.3 \u00b1 72.19, p &lt; 0.05, respectively) while no differences were found in their Cys-DA. Nonetheless, Cys-DA\/DOPAC ratio (0.213 \u00b1 0.024, p &lt; 0.05) and hsp27 levels (1073.0 \u00b1 136.4, p &lt; 0.05) were significantly higher. To the best of our knowledge, the c.2614G&gt;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\u2019s 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.<\/jats:p>","DOI":"10.3390\/genes14071320","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T02:05:02Z","timestamp":1687745102000},"page":"1320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Upregulation of Heat-Shock Protein (hsp)-27 in a Patient with Heterozygous SPG11 c.1951C&gt;T and SYNJ1 c.2614G&gt;T Mutations Causing Clinical Spastic Paraplegia"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3938-7698","authenticated-orcid":false,"given":"Juan","family":"Garc\u00eda-Carmona","sequence":"first","affiliation":[{"name":"Department of Neurology, Santa Lucia University Hospital, 30202 Cartagena, Spain"},{"name":"Group of Clinical & Experimental Pharmacology, Institute for Biomedical Research of Murcia (IMIB), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaqu\u00edn","family":"Amores-Iniesta","sequence":"additional","affiliation":[{"name":"Department of Animal Health, University of Murcia, 30100 Murcia, Spain"},{"name":"Group of Mycoplasmosis, Epidemiology and Pathogen-Host Interaction, Institute for Biomedical Research of Murcia (IMIB), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Soler-Usero","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry, University of Castilla-Le\u00f3n, 09001 Burgos, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Cerd\u00e1n-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Santa Lucia University Hospital, 30202 Cartagena, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1653-8131","authenticated-orcid":false,"given":"Javier","family":"Navarro-Zaragoza","sequence":"additional","affiliation":[{"name":"Group of Clinical & Experimental Pharmacology, Institute for Biomedical Research of Murcia (IMIB), 30120 Murcia, Spain"},{"name":"Department of Pharmacology, University of Murcia, 30100 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"L\u00f3pez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Santa Lucia University Hospital, 30202 Cartagena, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Soria-Torrecillas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Santa Lucia University Hospital, 30202 Cartagena, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ainhoa","family":"Ballesteros-Arenas","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry, University of Castilla-Le\u00f3n, 09001 Burgos, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"P\u00e9rez-Vicente","sequence":"additional","affiliation":[{"name":"Department of Neurology, Santa Lucia University Hospital, 30202 Cartagena, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1576-7760","authenticated-orcid":false,"given":"Pilar","family":"Almela","sequence":"additional","affiliation":[{"name":"Group of Clinical & Experimental Pharmacology, Institute for Biomedical Research of Murcia (IMIB), 30120 Murcia, Spain"},{"name":"Department of Pharmacology, University of Murcia, 30100 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Meyyazhagan, A., and Orlacchio, A. 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