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Andre Bento AbreuLaboratory of NeurobiologyExperimental NeurologyDepartment of NeurosciencesVesalius Research Center - VIBK.U.Leuven
BSc of Biochemistry, University of Coimbra, Portugal, 2002PhD in Biochemistry and Cellular Biology, University of Salamanca, Spain, 2008
Postdoctoral researcher at the K. U. Leuven, since 2009
E-mail: [email protected]: +32 (16) 33 07 63
KeywordsAmyotrophic Lateral Sclerosis, Elp3, HDAC6, tubulin acetylation, SOD1G93A mouse
ScienceAmyotrophic Lateral Sclerosis (ALS) is the most common motor neuron disorder of adulthood and considered one of the most dramatic diseases encountered in human medicine. ALS is a progressive disease and is fatal for most patients after 3 to 5 years. The lifetime risk to attract ALS is rather high, approximately 1 in 400. Although mutations in the SOD1, TARDBP and FUS genes have been identified in ALS patients and glutamate-mediated excitotoxicity is known to contribute to the progression of the disease, the majority of ALS cases have an unknown cause. Currently, there is no cure for ALS. Recently, a polymorphism in the ELP3 gene has been associated with protection against amyotrophic lateral sclerosis (ALS). Moreover, two loss-of-function mutations in the Drosophila ELP3 were identified to induce profound axonal and synaptic defects, and the knock-down of Elp3 in zebrafish induced motor axonal abnormalities. Elp3, known to acetylate histones, has been recently described to acetylate alpha-tubulin. The deacetylation of alpha-tubulin is mainly exerted by HDAC6 and its inhibition compensates for the transport deficit in Huntington’s disease by increasing tubulin acetylation. Acetylation of alpha-tubulin is a major determinant of axonal transport, which is pivotal in neurodegeneration, particularly in motor neurons. We intend to investigate whether the modulation of microtubule acetylation in the spinal cord of an ALS mouse model has a protective effect against neurodegeneration. To this end, Elp3 overexpression and HDAC6 knock-down in this tissue will be achieved by generating tissue-specific transgenic mice and by intraventricular AAV9-mediated gene delivery. Elp3 knock-out mice will also be generated to assess whether lacking of Elp3 deteriorates the SOD1G93A mouse phenotype. Although ALS pathology is most certainly a multi-factorial disease, our study can provide major insight on the role played by tubulin acetylation in this disease. Modulation of tubulin acetylation may represent a new strategy for the treatment of ALS and can be a common feature among different neurodegenerative diseases.
Selected PublicationsBento-Abreu A, Van Damme P, Van Den Bosch L, Robberecht W. The neurobiology of amyotrophic lateral sclerosis. Eur J Neurosci. 2010 Jun 7. [Epub ahead of print]PMID: 20529130
