D1 dopamine receptor stimulation impairs striatal proteasome activity in Parkinsonism through 26S proteasome disassembly.
Neurobiology of Disease. 2015-06-01; 78: 77-87
DOI: 10.1016/j.nbd.2015.02.024
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1. Neurobiol Dis. 2015 Jun;78:77-87. doi: 10.1016/j.nbd.2015.02.024. Epub 2015 Mar
10.
D1 dopamine receptor stimulation impairs striatal proteasome activity in
Parkinsonism through 26S proteasome disassembly.
Barroso-Chinea P(1), Thiolat ML(1), Bido S(1), Martinez A(1), Doudnikoff E(1),
Baufreton J(1), Bourdenx M(1), Bloch B(1), Bezard E(2), Martin-Negrier ML(1).
Author information:
(1)Univ. de Bordeaux, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des
Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
(2)Univ. de Bordeaux, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des
Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France. Electronic
address: .
Among the mechanisms underlying the development of L-dopa-induced dyskinesia
(LID) in Parkinson’s disease, complex alterations in dopamine signaling in D1
receptor (D1R)-expressing medium spiny striatal neurons have been unraveled such
as, but not limited to, dysregulation of D1R expression, lateral diffusion,
intraneuronal trafficking, subcellular localization and desensitization, leading
to a pathological anchorage of D1R at the plasma membrane. Such anchorage is
partly due to a decreased proteasomal activity that is specific of the
L-dopa-exposed dopamine-depleted striatum, results from D1R activation and
feeds-back the D1R exaggerated cell surface abundance. The precise mechanisms by
which L-dopa affects striatal proteasome activity remained however unknown. We
here show, in a series of in vitro ex vivo and in vivo models, that such rapid
modulation of striatal proteasome activity intervenes through D1R-mediated
disassembly of the 26S proteasome rather than change in transcription or
translation of proteasome or proteasome subunits intraneuronal relocalization.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.nbd.2015.02.024
PMID: 25766677 [Indexed for MEDLINE]