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The beta-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice

Ong-Palsson, E; Njavro, JR; Wilson, Y; Pigoni, M; Schmidt, A; Mueller, SA; Meyer, M; ... Lichtenthaler, SF; + view all (2021) The beta-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice. Molecular Neurobiology 10.1007/s12035-021-02660-y. Green open access

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Abstract

The membrane protein seizure 6–like (SEZ6L) is a neuronal substrate of the Alzheimer’s disease protease BACE1, and little is known about its physiological function in the nervous system. Here, we show that SEZ6L constitutive knockout mice display motor phenotypes in adulthood, including changes in gait and decreased motor coordination. Additionally, SEZ6L knockout mice displayed increased anxiety-like behaviour, although spatial learning and memory in the Morris water maze were normal. Analysis of the gross anatomy and proteome of the adult SEZ6L knockout cerebellum did not reveal any major differences compared to wild type, indicating that lack of SEZ6L in other regions of the nervous system may contribute to the phenotypes observed. In summary, our study establishes physiological functions for SEZ6L in regulating motor coordination and curbing anxiety-related behaviour, indicating that aberrant SEZ6L function in the human nervous system may contribute to movement disorders and neuropsychiatric diseases.

Type: Article
Title: The beta-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s12035-021-02660-y
Publisher version: https://doi.org/10.1007/s12035-021-02660-y
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, Seizure protein 6, DigiGait, Rotarod, Anxiety, Spatial learning and memory, RANDOMIZED-TRIAL, BACE1, VERUBECESTAT, MYELINATION, GUIDANCE, CHL1, GENE, L1
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10141410
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