title: Complexin-1 and Foxp1 Expression Changes Are Novel Brain Effects of Alpha-Synuclein Pathology.
abstract: 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.
authors.affiliation: Exp. Neurology, Goethe University Medical School, Building 89, Theodor Stern Kai 7, 60590, Frankfurt am Main, Germany.
authors.forename: Suzana
authors.initials: S
authors.lastname: Gispert
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurz
authors.forename: Nadine
authors.initials: N
authors.lastname: Brehm
authors.forename: Katrin
authors.initials: K
authors.lastname: Rau
authors.forename: Michael
authors.initials: M
authors.lastname: Walter
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Georg
authors.initials: G
authors.lastname: Auburger
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D001933:Brain Stem / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008636:Mesencephalon / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D051844:alpha-Synuclein / Q000172:deficiency / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D033942:Adaptor Proteins, Vesicular Transport; D051858:Forkhead Transcription Factors; C432917:Foxp1 protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D051844:alpha-Synuclein; C095992:complexin I
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