In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 24, No. 34 ( 2004-08-25), p. 7445-7454
Kurzfassung:
Parkinson's disease pathogenesis proceeds through several phases, culminating in the loss of dopaminergic neurons of the substantia nigra (SN). Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of oxidative SN injury is frequently used to study degeneration of dopaminergic neurons in mice and non-human primates, an understanding of the temporal sequence of molecular events from inhibition of mitochondrial complex 1 to neuronal cell death is limited. Here, microarray analysis and integrative data mining were used to uncover pathways implicated in the progression of changes in dopaminergic neurons after MPTP administration. This approach enabled the identification of small, yet consistently significant, changes in gene expression within the SN of MPTP-treated animals. Such an analysis disclosed dysregulation of genes in three main areas related to neuronal function: cytoskeletal stability and maintenance, synaptic integrity, and cell cycle and apoptosis. The discovery and validation of these alterations provide molecular evidence for an evolving cascade of injury, dysfunction, and cell death.
Materialart:
Online-Ressource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.4204-03.2004
Sprache:
Englisch
Verlag:
Society for Neuroscience
Publikationsdatum:
2004
ZDB Id:
1475274-8
SSG:
12
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