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.