Microtubule Alterations Occur Early in Experimental Parkinsonism and The Microtubule Stabilizer Epothilone D Is Neuroprotective

被引：102

作者：

Cartelli, Daniele ^{[1
]}

Casagrande, Francesca ^{[1
]}

Busceti, Carla Letizia ^{[2
]}

Bucci, Domenico ^{[2
]}

Molinaro, Gemma ^{[2
]}

Traficante, Anna ^{[2
]}

Passarella, Daniele ^{[3
]}

Giavini, Erminio ^{[1
]}

Pezzoli, Gianni ^{[4
]}

Battaglia, Giuseppe ^{[2
]}

Cappelletti, Graziella ^{[1
]}

机构：

[1] Univ Milan, Dept Biosci, Milan, Italy

[2] IRCCS Neuromed, Pozzilli, IS, Italy

[3] Univ Milan, Dept Chem, Milan, Italy

[4] Ist Clin Perfezionamento, Parkinson Inst, Milan, Italy

来源：

SCIENTIFIC REPORTS | 2013年 / 3卷

关键词：

AXONAL-TRANSPORT; COGNITIVE DEFICITS; BRAIN TUBULIN; BETA-TUBULIN; MOUSE MODEL; IN-VITRO; DYNAMICS; NEURONS; MITOCHONDRIA; DYSFUNCTION;

D O I：

10.1038/srep01837

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 beta III 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 MTs is an early event specifically associated with dopaminergic neuron degeneration. Pharmacological stabilization of MTs may be a viable strategy for the management of parkinsonism.

引用

页数：10

共 61 条

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