We are studying the molecular mechanisms underlying Amyotrophic Lateral Sclerosis (ALS).
Motor Neuron Diseases (MNDs) including Amyotrophic Lateral Sclerosis (ALS) were first identified more than 130 years ago but our understanding on what causes these devastating diseases is still rudimentary.
Such poor understanding hinders the development of therapies that at the moment do not seem to be very effective.
MNDs encompass a group of inherited disorders characterized by selective dysfunction and death of motor neurons leading to spasticity, muscle atrophy and paralysis.
Over the last decade, a growing number of neurodegenerative diseases, including polyglutamine diseases, Parkinson’s disease and tau-associated pathologies, have been modelled in the fruitfly Drosophila melanogaster.
Why study human neurodegeneration in flies?
Their small size, rapid generation time and low cost for maintenance as compared to mammalian models, have made them an attractive system.
Recently, we have generated a “fly model” for Amyotrophic Lateral Sclerosis (ALS) and we intend to use it to elucidate the molecular mechanisms underlying ALS.
We are confident that a better understanding of the molecular mechanisms responsible for the pathogenesis will open up the possibility to identify new targets for an effective therapeutic intervention.
Sanhueza M, Chai A, Smith C, McCray BA, Simpson TI, Taylor JP, Pennetta G. (2015) Network Analyses Reveal Novel Aspects of ALS Pathogenesis. PLoS Genet. 11(3):e1005107.
Sanhueza M, Zechini L, Gillespie T, Pennetta G. (2014) Gain-of-function mutations in the ALS8 causative gene VAPB have detrimental effects on neurons and muscles. Biol Open. 3(1):59-71.
Forrest S, Chai A, Sanhueza M, Marescotti M, Parry K, Georgiev A, Sahota V, Mendez-Castro R, Pennetta G. (2013) Increased levels of phosphoinositides cause neurodegeneration in a Drosophila model of amyotrophic lateral sclerosis. Hum Mol Genet. 22(13):2689-704.
Chen HJ, Anagnostou G, Chai A, Withers J, Morris A, Adhikaree J, Pennetta G, de Belleroche JS. (2010) Characterization of the properties of a novel mutation in VAPB in familial amyotrophic lateral sclerosis. J Biol Chem. 285(51):40266-81.
Chai A, Withers J, Koh YH, Parry K, Bao H, Zhang B, Budnik V, Pennetta G. (2008) hVAPB, the causative gene of a heterogeneous group of motor neuron diseases in humans, is functionally interchangeable with its Drosophila homologue DVAP-33A at the neuromuscular junction. Hum Mol Genet. 17(2):266-80.
Pennetta G, Hiesinger PR, Fabian-Fine R, Meinertzhagen IA, Bellen HJ. (2002) Drosophila VAP-33A directs bouton formation at neuromuscular junctions in a dosage-dependent manner. Neuron. 35(2):291-306.
Lloyd, T.E., Atkinson, R., Wu, M.N., Zhou, Y., Pennetta, G. and Bellen, H.J. (2002) Hrs regulates endosomal maturation and tyrosine kinase receptor signaling in Drosophila. Cell 108: 261-269.
Pennetta, G., Hiesinger, P.R., Fabian-Fine, R., Meinertzhagen, I.A. and Bellen, H. J. (2002). Drosophila VAP-33A directs bouton formation at neuromuscular junctions in a dosage- dependent manner. Neuron, 35: 281-306 (Cover).
Chai, A., Withers, J.P.J., Koh, Y.H., Zhang, B., Budnik, V., Pennetta, G. (2008). hVAPB, the causative gene of a heterogeneous group of motor neuron diseases in humans, is functionally interchangeable with its Drosophila homologue DVAP-33A at the Neuromuscular Junction. Human Molecular Genetics 17: 266-280.