Complexin-1 and Foxp1 Expression Changes Are Novel Brain Effects of Alpha-Synuclein PathologyReportar como inadecuado

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Molecular Neurobiology

, Volume 52, Issue 1, pp 57–63

First Online: 12 August 2014Received: 15 April 2014Accepted: 31 July 2014


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.

KeywordsParkinson’s disease Alpha-synuclein Midbrain-brainstem expression changes Presynaptic vesicles Complexin-1 Foxp1  Download fulltext PDF

Autor: Suzana Gispert - Alexander Kurz - Nadine Brehm - Katrin Rau - Michael Walter - Olaf Riess - Georg Auburger


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