MicroRNA and proteome expression profiling in early-symptomatic α-synuclein(A30P)-transgenic mice.

Abstract

The α-synuclein has been implicated in the pathophysiology of Parkinson's disease (PD), because mutations in the alpha-synuclein gene cause autosomal-dominant hereditary PD and fibrillary aggregates of alpha-synuclein are the major component of Lewy bodies. Since presynaptic accumulation of α-synuclein aggregates may trigger synaptic dysfunction and degeneration, we have analyzed alterations in synaptosomal proteins in early symptomatic α-synuclein(A30P)-transgenic mice by two-dimensional differential gel electrophoresis. Moreover, we carried out microRNA expression profiling using microfluidic chips, as microRNA have recently been shown to regulate synaptic plasticity in rodents and to modulate polyglutamine-induced protein aggregation and neurodegeneration in flies. Differentially expressed proteins in α-synuclein(A30P)-transgenic mice point to alterations in mitochondrial function, actin dynamics, iron transport, and vesicle exocytosis, thus partially resembling findings in PD patients. Oxygen consumption of isolated brain mitochondria, however, was not reduced in mutant mice. Levels of several microRNA (miR-10a, -10b, -212, -132, -495) were significantly altered. One of them (miR-132) has been reported to be highly inducible by growth factors and to be a key regulator of neurite outgrowth. Moreover, miR-132-recognition sequences were detected in the mRNA transcripts of two differentially expressed proteins. MicroRNA may thus represent novel biomarkers for neuronal malfunction and potential therapeutic targets for human neurodegenerative diseases.

• Authors: Frank Gillardon, Matthias Mack, Wolfgang Rist, Cathrin Schnack, Martin Lenter, Tobias Hildebrandt, Bastian Hengerer
• Journal: Proteomics. Clinical applications (Proteomics Clin Appl) Vol. 2 Issue 5 Pg. 697-705 (May 2008) ISSN: 1862-8346 [Print] Germany
• PMID: 21136867 (Publication Type: Journal Article)
• Copyright: Copyright © 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.