TY - JOUR
T1 - Microtubule alterations occur early in experimental parkinsonism and the microtubule stabilizer Epothilone D is neuroprotective
AU - Cartelli, Daniele
AU - Casagrande, Francesca
AU - Busceti, Carla Letizia
AU - Bucci, Domenico
AU - Molinaro, Gemma
AU - Traficante, Anna
AU - Passarella, Daniele
AU - Giavini, Erminio
AU - Pezzoli, Gianni
AU - Battaglia, Giuseppe
AU - Cappelletti, Graziella
N1 - Funding Information:
The authors are grateful to Dr. Alida Amadeo and Dr. Carmelita De Gregorio (Università degli Studi di Milano) for technical support and helpful discussions, and Dr. Jennifer S. Hartwig for reading and editing the manuscript. This work was supported by Fondazione Grigioni per il Morbo di Parkinson, Milan, Italy (to G.C.), and ‘‘Dote ricerca’’, FSE, Regione Lombardia (to D.C.).
PY - 2013
Y1 - 2013
N2 - The role of microtubule (MT) dysfunction in Parkinson's disease is emerging. It is still unknown whether it is a cause or a consequence of neurodegeneration. Our objective was to assess whether alterations of MT stability precede or follow axonal transport impairment and neurite degeneration in experimental parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in C57Bl mice. MPTP induced a time- and dose-dependent increase in fibres with altered mitochondria distribution, and early changes in cytoskeletal proteins and MT stability. Indeed, we observed significant increases in neuron-specific βIII tubulin and enrichment of deTyr tubulin in dopaminergic neurons. Finally, we showed that repeated daily administrations of the MT stabilizer Epothilone D rescued MT defects and attenuated nigrostriatal degeneration induced by MPTP. These data suggest that alteration of ΜΤs is an early event specifically associated with dopaminergic neuron degeneration. Pharmacological stabilization of MTs may be a viable strategy for the management of parkinsonism.
AB - The role of microtubule (MT) dysfunction in Parkinson's disease is emerging. It is still unknown whether it is a cause or a consequence of neurodegeneration. Our objective was to assess whether alterations of MT stability precede or follow axonal transport impairment and neurite degeneration in experimental parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in C57Bl mice. MPTP induced a time- and dose-dependent increase in fibres with altered mitochondria distribution, and early changes in cytoskeletal proteins and MT stability. Indeed, we observed significant increases in neuron-specific βIII tubulin and enrichment of deTyr tubulin in dopaminergic neurons. Finally, we showed that repeated daily administrations of the MT stabilizer Epothilone D rescued MT defects and attenuated nigrostriatal degeneration induced by MPTP. These data suggest that alteration of ΜΤs is an early event specifically associated with dopaminergic neuron degeneration. Pharmacological stabilization of MTs may be a viable strategy for the management of parkinsonism.
UR - http://www.scopus.com/inward/record.url?scp=84878719968&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878719968&partnerID=8YFLogxK
U2 - 10.1038/srep01837
DO - 10.1038/srep01837
M3 - Article
C2 - 23670541
AN - SCOPUS:84878719968
VL - 3
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 1837
ER -