{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:16:37Z","timestamp":1771028197800,"version":"3.50.1"},"reference-count":74,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>We investigated the effects of intrathecal administration of a novel toxin, CTK 01512\u20102, in a mouse model of Huntington's disease. We asked whether spinal cord neurons can represent a therapeutic target, given that the spinal cord seems to be involved in motor symptoms of Huntington's disease. Pharmacological approaches focusing on the spinal cord and skeletal muscles might represent a more feasible strategy than a high\u2010risk brain intervention.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>We provided evidence of a novel, local, neuroprotective effect of CTK 01512\u20102, paving a path for the development of approaches to treat motor symptoms of Huntington's disease beyond the brain.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Ph\u03b11\u03b2 is a neurotoxin from the venom of the <jats:italic>Phoneutria nigriventer<\/jats:italic> spider, available as CTK 01512\u20102, a recombinant peptide. Owing to its antinociceptive and analgesic properties, CTK 01512\u20102 has been described to alleviate neuroinflammatory responses. Despite the diverse actions of CTK 01512\u20102 on the nervous system, little is known regarding its neuroprotective effect, especially in neurodegenerative conditions such as Huntington's disease (HD), a genetic movement disorder without cure. Here, we investigated whether CTK 01512\u20102 has a neuroprotective effect in a mouse model of HD. We hypothesized that spinal cord neurons might represent a therapeutic target, because the spinal cord seems to be involved in the motor symptoms of HD (BACHD) mice. We treated BACHD mice with CTK 01512\u20102 by intrathecal injection and performed in vivo motor behavioural and morphological analyses in the CNS (brain and spinal cord) and muscles. Our data showed that intrathecal injection of CTK 01512\u20102 significantly improved motor performance in the open field task. CTK 01512\u20102 protected neurons in the spinal cord (but not in the brain) from death, suggesting a local effect. CTK 01512\u20102 exerted its neuroprotective effect by inhibiting BACHD neuronal apoptosis, as revealed by a reduction in caspase\u20103 in the spinal cord. CTK 01512\u20102 was also able to revert BACHD muscle atrophy. In conclusion, our data suggest a novel role for CTK 01512\u20102 acting directly in the spinal cord to ameliorate morphofunctional aspects of spinal cord neurons and muscles and improve the performance of BACHD mice in motor behavioural tests. Given that HD shares similar symptoms with many neurodegenerative conditions, the findings presented herein might also be applicable to other disorders.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep090327","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T05:39:45Z","timestamp":1651124385000},"page":"933-945","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Neuroprotective effect of CTK 01512\u20102 recombinant toxin at the spinal cord in a model of Huntington's disease"],"prefix":"10.1113","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5788-6223","authenticated-orcid":false,"given":"Julliane V.","family":"Joviano\u2010Santos","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biologia da Neurotransmiss\u00e3o Departamento de Morfologia Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais Brazil  Belo Horizonte MG"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscila A. 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G.","family":"Machado","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia da Neurotransmiss\u00e3o Departamento de Morfologia Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais Brazil  Belo Horizonte MG"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kivia B.","family":"Soares","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia da Neurotransmiss\u00e3o Departamento de Morfologia Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais Brazil  Belo Horizonte MG"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina S.","family":"Ladeira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia da Neurotransmiss\u00e3o Departamento de Morfologia Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais Brazil  Belo Horizonte MG"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1508-3801","authenticated-orcid":false,"given":"Andre R.","family":"Massensini","sequence":"additional","affiliation":[{"name":"N\u00facleo de Neuroci\u00eancias Departamento de Fisiologia e Biof\u00edsica Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais  Belo Horizonte MG Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus V.","family":"Gomez","sequence":"additional","affiliation":[{"name":"IEP Santa Casa  Belo Horizonte MG Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline S.","family":"Miranda","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Neurobiologia Departamento de Morfologia Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais  Belo Horizonte MG Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan C.","family":"T\u00e1pia","sequence":"additional","affiliation":[{"name":"Escuela de Medicina Universidad de Talca  Talca Chile"},{"name":"Department of Molecular and Cellular Biology Harvard University  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5392-1266","authenticated-orcid":false,"given":"Cristina","family":"Guatimosim","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia da Neurotransmiss\u00e3o Departamento de Morfologia Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais Brazil  Belo Horizonte MG"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0b013e318205b249"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.npep.2019.101980"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2021.08.016"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2015.12.013"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2017.139"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-06-01649.1991"},{"key":"e_1_2_9_8_1","first-page":"117","article-title":"Huntington disease. 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