Now free in PMC--Drosophila model included in study relating microtubule acetylation to reduction of deficits caused by mutations in LRRK2

Godena VK, Brookes-Hocking N, Moller A, Shaw G, Oswald M, Sancho RM, Miller CC, Whitworth AJ, De Vos KJ. Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations. Nat Commun. 2014 Oct 15;5:5245. PMID: 25316291; PMCID: PMC4208097.

From the abstract: "Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease. LRRK2 is a multifunctional protein affecting many cellular processes and has been described to bind microtubules. Defective microtubule-based axonal transport is hypothesized to contribute to Parkinson's disease, but whether LRRK2 mutations affect this process to mediate pathogenesis is not known. Here we find that LRRK2 containing pathogenic Roc-COR domain mutations (R1441C, Y1699C) preferentially associates with deacetylated microtubules, and inhibits axonal transport in primary neurons and in Drosophila ... In vivo knockdown of the deacetylases HDAC6 and Sirt2, or administration of TSA rescues both axonal transport and locomotor behavior. ..."