Identification of bilateral changes in T1D1 expression in the 6-OHDA rat model of Parkinson's disease

dc.contributor.authorProft, Juliane
dc.contributor.authorFaraji, Jamshid
dc.contributor.authorRobbins, Jerrah C.
dc.contributor.authorZucchi, Fabiola C. R.
dc.contributor.authorZhao, Xiaoxi
dc.contributor.authorMetz, Gerlinde A. S.
dc.contributor.authorBraun, Janice E. A.
dc.descriptionSherpa Romeo green journal: open accessen_US
dc.description.abstractParkinson’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.en_US
dc.identifier.citationProft, 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.0026045en_US
dc.publisherPublic Library of Scienceen_US
dc.publisher.departmentDepartment of Neuroscienceen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.institutionGolestan University of Medical Sciencesen_US
dc.subjectParkinson's diseaseen_US
dc.subjectParkinson's disease -- Animal modelsen_US
dc.subjectT1D1 expressionen_US
dc.subjectMolecular chaperonesen_US
dc.subjectJ proteinen_US
dc.titleIdentification of bilateral changes in T1D1 expression in the 6-OHDA rat model of Parkinson's diseaseen_US
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