Golestan University of Medical Sciences Repository

Identification of bilateral changes in TID1 expression in the 6-OHDA rat model of Parkinson's disease

Proft, J. and Faraji, J. and Robbins, J.C. and Zucchi, F.C.R. and Zhao, X. and Metz, G.A. and Braun, J.E.A. (2011) Identification of bilateral changes in TID1 expression in the 6-OHDA rat model of Parkinson's disease. PLoS ONE, 6 (10). ISSN 19326203 (ISSN)

PDF - Published Version
Download (2MB) | Preview


Parkinson's disease (PD) is a common neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra and the aggregation of α-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 CSPα, Hsp40, Hsp70, Hsc70 and PrP C 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. © 2011 Proft et al.

Item Type: Article
Additional Information: Unmapped bibliographic data: C7 - e26045 [EPrints field already has value set] LA - English [Field not mapped to EPrints] J2 - PLoS ONE [Field not mapped to EPrints] C2 - 22016808 [Field not mapped to EPrints] AD - Hotchkiss Brain Institute, Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada [Field not mapped to EPrints] AD - Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Canada [Field not mapped to EPrints] AD - Neuroscience Research Centre, Golestan University of Medical Sciences, Gorgan, Iran [Field not mapped to EPrints] DB - Scopus [Field not mapped to EPrints]
Uncontrolled Keywords: alpha synuclein, caspase 3, chaperone, heat shock protein 25, heat shock protein 40, heat shock protein 70, heat shock protein 90, oxidopamine, protein DnaJ, protein TID1, unclassified drug, 1 methyl 4 phenylpyridinium, alpha synuclein, heat shock protein 40, oxidopamine, animal cell culture, animal experiment, animal model, animal tissue, article, brain region, controlled study, disease course, dopaminergic nerve cell, female, Lewy body, molecular mechanics, motor dysfunction, motor performance, nonhuman, Parkinson disease, pathogenesis, protein aggregation, protein analysis, protein conformation, protein expression, protein family, protein folding, rat, substantia nigra, animal, chemistry, disease model, drug effect, gene expression regulation, homeostasis, Long Evans rat, metabolism, mitochondrion, molecular weight, mouse, pathology, pathophysiology, psychomotor performance, signal transduction, tumor cell line, Rattus, 1-Methyl-4-phenylpyridinium, alpha-Synuclein, Animals, Cell Line, Tumor, Disease Models, Animal, Female, Gene Expression Regulation, Homeostasis, HSP40 Heat-Shock Proteins, Mice, Mitochondria, Molecular Weight, Oxidopamine, Parkinson Disease, Psychomotor Performance, Rats, Rats, Long-Evans, Signal Transduction
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
موارد کلی
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 15 Apr 2015 04:08
Last Modified: 16 May 2015 11:12
URI: http://eprints.goums.ac.ir/id/eprint/2088

Actions (login required)

View Item View Item