dc.contributor.author | Zeng, Bai-Yun | |
dc.contributor.author | Iravani, Mahmoud M. | |
dc.contributor.author | Lin, S. T. | |
dc.contributor.author | Irifune, M. | |
dc.contributor.author | Kuoppamaki, M. | |
dc.contributor.author | Al-Barghouthy, G. | |
dc.contributor.author | Smith, L. | |
dc.contributor.author | Jackson, M. J. | |
dc.contributor.author | Rose, S. | |
dc.contributor.author | Medhurst, A.D. | |
dc.contributor.author | Jenner, P. | |
dc.date.accessioned | 2013-12-18T12:00:15Z | |
dc.date.available | 2013-12-18T12:00:15Z | |
dc.date.issued | 2006-04 | |
dc.identifier.citation | Zeng , B-Y , Iravani , M M , Lin , S T , Irifune , M , Kuoppamaki , M , Al-Barghouthy , G , Smith , L , Jackson , M J , Rose , S , Medhurst , A D & Jenner , P 2006 , ' MPTP treatment of common marmosets impairs proteasomal enzyme activity and decreases expression of structural and regulatory elements of the 26S proteasome ' , European Journal of Neuroscience , vol. 23 , no. 7 , pp. 1766-1774 . https://doi.org/10.1111/j.1460-9568.2006.04718.x | |
dc.identifier.issn | 0953-816X | |
dc.identifier.other | ORCID: /0000-0002-4905-9682/work/32997585 | |
dc.identifier.uri | http://hdl.handle.net/2299/12404 | |
dc.description.abstract | Dysfunction of the ubiquitin-proteasome system occurs in the substantia nigra (SN) in Parkinson's disease (PD). However, it is unknown whether this is a primary cause or a secondary consequence of other components of the pathogenic process. We have investigated in nonhuman primates whether initiating cell death through mitochondrial complex I inhibition using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) altered proteasomal activity or the proteasomal components in the SN. Chymotrypsin-like, trypsin-like and peptidylglutamyl-peptide hydrolase (PGPH) activating of 20S proteasome were decreased in SN homogenates of MPTP-treated marmosets compared to naive animals. Western blotting revealed a marked decrease in the expression of 20S-alpha subunits, but no change in 20S-beta subunits in the SN of MPTP-treated marmoset compared to naive animals. There was a marked decrease in the expression of the proteasome activator 700 (PA700) and proteasome activator 28 (PA28) regulatory complexes. The 20S-alpha 4 subunit immunoreactivity was decreased in the nucleus of colocalized tyrosine hydroxylase (TH)-positive cells of MPTP-treated animals compared to naive animals but no difference in the intensity of 20S-beta 1i subunit staining. Immunoreactivity for PA700-Rpt5 and PA28-alpha subunits within surviving TH-positive cells of MPTP-treated marmoset was reduced compared to naive controls. Overall, the changes in proteasomal function and structure occurring follow MPTP-induced destruction of the SN in common marmosets were very similar to those found in PD. This suggests that altered proteasomal function in PD could be a consequence of other pathogenic processes occurring in SN as opposed to initiating cell death as previously suggested. | en |
dc.format.extent | 9 | |
dc.language.iso | eng | |
dc.relation.ispartof | European Journal of Neuroscience | |
dc.subject | common marmoset | |
dc.subject | MPTP | |
dc.subject | Parkinson's disease | |
dc.subject | proteasome activity | |
dc.subject | proteasome subunits | |
dc.subject | ubiquitin-proteasome pathway | |
dc.subject | SPORADIC PARKINSONS-DISEASE | |
dc.subject | MITOCHONDRIAL COMPLEX-I | |
dc.subject | OXIDIZED PROTEINS | |
dc.subject | OXIDATIVE DAMAGE | |
dc.subject | ALPHA-SYNUCLEIN | |
dc.subject | 20S PROTEASOME | |
dc.subject | ANTIGEN PRESENTATION | |
dc.subject | INHIBITION CAUSES | |
dc.subject | SUBSTANTIA-NIGRA | |
dc.subject | LEWY BODIES | |
dc.title | MPTP treatment of common marmosets impairs proteasomal enzyme activity and decreases expression of structural and regulatory elements of the 26S proteasome | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Centre for Research in Mechanisms of Disease and Drug Discovery | |
dc.contributor.institution | Department of Clinical, Pharmaceutical and Biological Science | |
dc.contributor.institution | Basic and Clinical Science Unit | |
dc.contributor.institution | Centre for Health Services and Clinical Research | |
dc.description.status | Peer reviewed | |
rioxxterms.versionofrecord | 10.1111/j.1460-9568.2006.04718.x | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |