Microtubule Alterations Occur Early in Experimental Parkinsonism and the Microtubule Stabilizer Epothilone D is Neuroprotective

Overview

Journal Sci Rep

Specialty Science

Date 2013 May 15

PMID 23670541

Citations 58

Authors

Daniele Cartelli

Francesca Casagrande

Carla Letizia Busceti

Domenico Bucci

Gemma Molinaro

Anna Traficante

Daniele Passarella

Erminio Giavini

Gianni Pezzoli

Giuseppe Battaglia

Graziella Cappelletti

Affiliations

Soon will be listed here.

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.

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