Complexin-1 and foxp1 expression changes are novel brain effects of alpha-synuclein pathology

  • As the second most frequent neurodegenerative disorder of the aging population, Parkinson’s disease (PD) is characterized by progressive deficits in spontaneous movement, atrophy of dopaminergic midbrain neurons and aggregation of the protein alpha-synuclein (SNCA). To elucidate molecular events before irreversible cell death, we studied synucleinopathy-induced expression changes in mouse brain and identified 49 midbrain/brainstem-specific transcriptional dysregulations. In particular complexin-1 (Cplx1), Rabl2a and 14-3-3epsilon (Ywhae) downregulation, as well as upregulation of the midbrain-specific factor forkhead box P1 (Foxp1) and of Rabgef1, were interesting as early mRNA level effects of alpha-synuclein triggered pathology. The protein levels of complexin-1 were elevated in midbrain/brainstem tissue of mice with A53T-SNCA overexpression and of mice with SNCA-knockout. The response of CPLX1 and Foxp1 levels to SNCA deficiency supports the notion that these factors are regulated by altered physiological function of alpha-synuclein. Thus, their analysis might be useful in PD stages before the advent of Lewy pathology. Because both alpha-synuclein and complexin-1 modulate vesicle release, our findings support presynaptic dysfunction as an early event in PD pathology.
Author:Suzana Gispert, Alexander Kurz, Nadine Brehm, Katrin Rau, Michael Walter, Olaf Rieß, Georg AuburgerORCiDGND
Pubmed Id:
Parent Title (English):Molecular neurobiology
Publisher:Humana Press
Place of publication:Totowa, NJ
Document Type:Article
Year of Completion:2014
Date of first Publication:2014/08/12
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/07/11
Tag:Alpha-synuclein; Complexin-1; Foxp1; Midbrain/brainstem expression changes; Parkinson’s disease; Presynaptic vesicles
Page Number:7
First Page:57
Last Page:63
Open Access: This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0