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dc.contributor.authorZeng, Bai-Yun
dc.contributor.authorIravani, Mahmoud M.
dc.contributor.authorLin, S. T.
dc.contributor.authorIrifune, M.
dc.contributor.authorKuoppamaki, M.
dc.contributor.authorAl-Barghouthy, G.
dc.contributor.authorSmith, L.
dc.contributor.authorJackson, M. J.
dc.contributor.authorRose, S.
dc.contributor.authorMedhurst, A.D.
dc.contributor.authorJenner, P.
dc.identifier.citationZeng , 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 .
dc.identifier.otherPURE: 735245
dc.identifier.otherPURE UUID: 165f4675-aa21-410e-b2a3-c768221f13ab
dc.identifier.otherWOS: 000236457500010
dc.identifier.otherScopus: 33645450436
dc.identifier.otherORCID: /0000-0002-4905-9682/work/32997585
dc.description.abstractDysfunction 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.relation.ispartofEuropean Journal of Neuroscience
dc.subjectcommon marmoset
dc.subjectParkinson's disease
dc.subjectproteasome activity
dc.subjectproteasome subunits
dc.subjectubiquitin-proteasome pathway
dc.subject20S PROTEASOME
dc.subjectLEWY BODIES
dc.titleMPTP treatment of common marmosets impairs proteasomal enzyme activity and decreases expression of structural and regulatory elements of the 26S proteasomeen
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionPharmacology and Clinical Science Research
dc.contributor.institutionNeurodegenerative Diseases
dc.contributor.institutionAgriculture, Veterinary and Food Sciences
dc.description.statusPeer reviewed
rioxxterms.typeJournal Article/Review

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