Identification of bilateral changes in T1D1 expression in the 6-OHDA rat model of Parkinson's disease
Loading...
Date
2011
Authors
Proft, Juliane
Faraji, Jamshid
Robbins, Jerrah C.
Zucchi, Fabiola C. R.
Zhao, Xiaoxi
Metz, Gerlinde A. S.
Braun, Janice E. A.
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
Abstract
Parkinson’s disease (PD) is a common neurodegenerative disease characterized by the loss of dopaminergic neurons in the
substantia nigra and the aggregation of a-synuclein into Lewy bodies. Existing therapies address motor dysfunction but do
not halt progression of the disease. A still unresolved question is the biochemical pathway that modulates the outcome of
protein misfolding and aggregation processes in PD. The molecular chaperone network plays an important defensive role
against cellular protein misfolding and has been identified as protective in experimental models of protein misfolding
diseases like PD. Molecular mechanisms underlying chaperone-neuroprotection are actively under investigation. Current
evidence implicates a number of molecular chaperones in PD including Hsp25, Hsp70 and Hsp90, however their precise
involvement in the neurodegenerative cascade is unresolved. The J protein family (DnaJ or Hsp40 protein family) has long
been known to be important in protein conformational processes. We assessed sensory and motor function of control and
PD rats and then evaluated the brain region-specific expression levels of select J proteins by Western analysis. Surprisingly,
we observed a widespread 26 kDa breakdown product of the J protein, TID1, (tumorous imaginal discs, mtHsp40 or DnaJ3)
in a 6-hydroxydopamine (6-OHDA) rat model of PD in which food handling, gait symmetry and sensory performance were
impaired. Greater behavioral deficits were associated with lower TID1 expression. Furthermore, direct application of either 6-
OHDA or MPP+ (1-methyl-4-phenylpyridinum) to CAD (CNS-derived catecholinaminergic neuronal cell line) cell cultures,
reduced TID1 expression levels. Our results suggest that changes in cellular TID1 are a factor in the pathogenesis of PD by
impeding functional and structural compensation and exaggerating neurodegenerative processes. In contrast, no changes
were observed in CSPa, Hsp40, Hsp70, Hsc70 and PrPC levels and no activation of caspase3 was observed. This study links
TID1 to PD and provides a new target for therapeutics that halts the PD progression.
Description
Sherpa Romeo green journal: open access
Keywords
Parkinson's disease , Parkinson's disease -- Animal models , Rats , T1D1 expression , Molecular chaperones , Neurodegenerative , J protein , 6-OHDA
Citation
Proft, J., Faraji, J., Robbins, J. C., Zucchi, F. C. R., Zhao, X., Metz, G. A. S., & Braun, J. E. A. (2011). Identification of bilateral changes in T1D1 expression in the 6-OHDA rat model of Parkinson's disease. PLoS ONE, 6(10), e20645. doi:10.1371/journal.pone.0026045