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.
Neuronal microtubules and proteins linked to Parkinson's disease: a relevant interaction? / A.M. Calogero, S. Mazzetti, G. Pezzoli, G. Cappelletti. - In: BIOLOGICAL CHEMISTRY. - ISSN 1437-4315. - 400:9(2019 Aug 27), pp. 1099-1112.
|Titolo:||Neuronal microtubules and proteins linked to Parkinson's disease: a relevant interaction?|
CALOGERO, ALESSANDRA MARIA ELENA (Primo) (Corresponding)
MAZZETTI, SAMANTA (Secondo)
CAPPELLETTI, GRAZIELLA (Ultimo) (Corresponding)
|Parole Chiave:||LRRK2; Parkin; Parkinson’s disease; microtubules; tubulin; α-Synuclein|
|Settore Scientifico Disciplinare:||Settore BIO/16 - Anatomia Umana|
Settore BIO/06 - Anatomia Comparata e Citologia
|Data di pubblicazione:||27-ago-2019|
|Data ahead of print / Data di stampa:||1-lug-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1515/hsz-2019-0142|
|Appare nelle tipologie:||01 - Articolo su periodico|
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