| First Author | Barroso-Chinea P | Year | 2015 |
| Journal | Neurobiol Dis | Volume | 78 |
| Pages | 77-87 | PubMed ID | 25766677 |
| Mgi Jnum | J:255107 | Mgi Id | MGI:6100355 |
| Doi | 10.1016/j.nbd.2015.02.024 | Citation | Barroso-Chinea P, et al. (2015) D1 dopamine receptor stimulation impairs striatal proteasome activity in Parkinsonism through 26S proteasome disassembly. Neurobiol Dis 78:77-87 |
| abstractText | 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. |
