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Microtubule Destabilization Paves the Way to Parkinson’s Disease

Abstract

Microtubules are dynamic structures normally associated to the cell division, during which they form the mitotic spindle, as well as to the initial phases of specification and polarization of various cell types, including neurons. Although microtubules could have a role in the death of many cells and tissues, the microtubule-based degenerative mechanisms have been poorly investigated; nevertheless, during the last two decades, many clues have been accumulated suggesting the importance of the microtubule system during neurodegeneration. Thus, the aim of this review is to analyse how the changes of the microtubule cytoskeleton, in terms of organization and dynamics, as well as the failure of the microtubule-dependent neuronal processes, as axonal transport, may play a pivotal role in the chain of events leading to Parkinson’s disease. Last but not least, since disease-modifying or neuroprotective strategies are a clinical priority in Parkinson’s disease, we will also present the hints about the concrete possibility of a microtubule-targeted therapy, which would have the potentiality to block the running degenerative events and to prompt the regeneration of the lost tissues.

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Acknowledgments

The authors are grateful to all the present and past members of the laboratory for their work, which have contributed in delineating the story here described, as well as for the interesting and stimulating discussions. 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.). The authors apologize for any possible involuntary paper omission.

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Cartelli, D., Cappelletti, G. Microtubule Destabilization Paves the Way to Parkinson’s Disease. Mol Neurobiol 54, 6762–6774 (2017). https://doi.org/10.1007/s12035-016-0188-5

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Keywords

  • Microtubule
  • Neuron health
  • Neurodegeneration
  • Parkinson’s disease
  • Tubulin-targeted therapy