Microtubule alterations occur early in experimental parkinsonism and the microtubule stabilizer Epothilone D is neuroprotective

Daniele Cartelli, Francesca Casagrande, Carla Letizia Busceti, Domenico Bucci, Gemma Molinaro, Anna Traficante, Daniele Passarella, Erminio Giavini, Gianni Pezzoli, Giuseppe Battaglia, Graziella Cappelletti

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Abstract

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.

Original languageEnglish (US)
Article number1837
JournalScientific Reports
Volume3
DOIs
StatePublished - Jun 12 2013

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Parkinsonian Disorders
Microtubules
Dopaminergic Neurons
Tubulin
Nerve Degeneration
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Axonal Transport
Cytoskeletal Proteins
Protein Stability
Neurites
Parkinson Disease
Mitochondria
desoxyepothilone B
Pharmacology
Neurons
4-phenyl-1,2,3,6-tetrahydropyridine

ASJC Scopus subject areas

  • General

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Microtubule alterations occur early in experimental parkinsonism and the microtubule stabilizer Epothilone D is neuroprotective. / Cartelli, Daniele; Casagrande, Francesca; Busceti, Carla Letizia; Bucci, Domenico; Molinaro, Gemma; Traficante, Anna; Passarella, Daniele; Giavini, Erminio; Pezzoli, Gianni; Battaglia, Giuseppe; Cappelletti, Graziella.

In: Scientific Reports, Vol. 3, 1837, 12.06.2013.

Research output: Contribution to journalArticle

Cartelli, D, Casagrande, F, Busceti, CL, Bucci, D, Molinaro, G, Traficante, A, Passarella, D, Giavini, E, Pezzoli, G, Battaglia, G & Cappelletti, G 2013, 'Microtubule alterations occur early in experimental parkinsonism and the microtubule stabilizer Epothilone D is neuroprotective', Scientific Reports, vol. 3, 1837. https://doi.org/10.1038/srep01837
Cartelli, Daniele ; Casagrande, Francesca ; Busceti, Carla Letizia ; Bucci, Domenico ; Molinaro, Gemma ; Traficante, Anna ; Passarella, Daniele ; Giavini, Erminio ; Pezzoli, Gianni ; Battaglia, Giuseppe ; Cappelletti, Graziella. / Microtubule alterations occur early in experimental parkinsonism and the microtubule stabilizer Epothilone D is neuroprotective. In: Scientific Reports. 2013 ; Vol. 3.
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