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Licensed Unlicensed Requires Authentication Published by De Gruyter July 19, 2019

Neuronal microtubules and proteins linked to Parkinson’s disease: a relevant interaction?

  • Alessandra M. Calogero EMAIL logo , Samanta Mazzetti , Gianni Pezzoli and Graziella Cappelletti ORCID logo EMAIL logo
From the journal Biological Chemistry

Abstract

Neuronal microtubules are key determinants of cell morphology, differentiation, migration and polarity, and contribute to intracellular trafficking along axons and dendrites. Microtubules are strictly regulated and alterations in their dynamics can lead to catastrophic effects in the neuron. Indeed, the importance of the microtubule cytoskeleton in many human diseases is emerging. Remarkably, a growing body of evidence indicates that microtubule defects could be linked to Parkinson’s disease pathogenesis. Only a few of the causes of the progressive neuronal loss underlying this disorder have been identified. They include gene mutations and toxin exposure, but the trigger leading to neurodegeneration is still unknown. In this scenario, the evidence showing that mutated proteins in Parkinson’s disease are involved in the regulation of the microtubule cytoskeleton is intriguing. Here, we focus on α-Synuclein, Parkin and Leucine-rich repeat kinase 2 (LRRK2), the three main proteins linked to the familial forms of the disease. The aim is to dissect their interaction with tubulin and microtubules in both physiological and pathological conditions, in which these proteins are overexpressed, mutated or absent. We highlight the relevance of such an interaction and suggest that these proteins could trigger neurodegeneration via defective regulation of the microtubule cytoskeleton.

Acknowledgments

The authors are grateful to Fondazione Grigioni per il Morbo di Parkinson, Milan, Italy, for the long-standing support to A.M.C, S.M., and G.C., and to BTN (Nervous Tissue Bank, Milan, sponsored by Fondazione Grigioni per il Morbo di Parkinson) for supplying human tissues. The authors thank Dr. Jennifer S. Hartwig and Dr. Milo J. Basellini for reading and editing the manuscript. The authors are also grateful to all the present and former group members for their contributions and apologize for each possible involuntary paper omission.

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Received: 2019-01-31
Accepted: 2019-06-24
Published Online: 2019-07-19
Published in Print: 2019-08-27

©2019 Walter de Gruyter GmbH, Berlin/Boston

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