Loss-of-function caused by mutations in the parkin gene (PARK2) lead to early-onset familial Parkinson's disease. Recently, mechanistic studies proved the ability of parkin in regulating mitochondria homeostasis and microtubule (MT) stability. Looking at these systems during aging of PARK2 knockout mice, we found that loss of parkin induced an accelerated (over)acetylation of MT system both in dopaminergic neuron cell bodies and fibers, localized in the substantia nigra and corpus striatum, respectively. Interestingly, in PARK2 knockout mice, changes of MT stability preceded the alteration of mitochondria transport. Moreover, in-cell experiments confirmed that loss of parkin affects mitochondria mobility and showed that this defect depends on MT system as it is rescued by paclitaxel, a well-known MT-targeted agent. Furthermore, both in PC12 neuronal cells and in patients' induced pluripotent stem cell-derived midbrain neurons, we observed that parkin deficiencies cause the fragmentation of stable MTs. Therefore, we suggest that parkin acts as a regulator of MT system during neuronal aging, and we endorse the hypothesis that MT dysfunction may be crucial in the pathogenesis of Parkinson's disease.
Parkin absence accelerates microtubule aging in dopaminergic neurons / D. Cartelli, A. Amadeo, A.M. Calogero, F.V.M. Casagrande, C. De Gregorio, M. Gioria, N. Kuzumaki, I. Costa, J. Sassone, A. Ciammola, N. Hattori, H. Okano, S. Goldwurm, L. Roybon, G. Pezzoli, G. Cappelletti. - In: NEUROBIOLOGY OF AGING. - ISSN 1558-1497. - 61(2018 Jan), pp. 66-74.
|Titolo:||Parkin absence accelerates microtubule aging in dopaminergic neurons|
CARTELLI, DANIELE (Primo)
CAPPELLETTI, GRAZIELLA (Ultimo) (Corresponding)
|Parole Chiave:||Aging; Dopaminergic neurons; Microtubule; Parkin; Parkinson's disease; Tubulin post-translational modifications|
|Settore Scientifico Disciplinare:||Settore BIO/06 - Anatomia Comparata e Citologia|
Settore BIO/16 - Anatomia Umana
|Data di pubblicazione:||gen-2018|
|Data ahead of print / Data di stampa:||dic-2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.neurobiolaging.2017.09.010|
|Appare nelle tipologie:||01 - Articolo su periodico|