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Projects. Life and Matter Sciences

Analysis using genetically modified mice of the possible role of alpha-synuclein in the pathogenesis of Huntington's disease

Lead Researcher: 
José Javier Lucas Lozano 

Research Centre: 
Centro de Biología Molecular "Severo Ochoa". CSIC-UAM. (Spain).
José LucasHuntington's disease (HD) is caused by polyglutamine expansion in the huntingtin protein that leads it to aggregate and form inclusion bodies (IBs). IBs are a common feature of neurodegenerative diseases. In the case of Parkinson's disease, they are formed by the alpha-synuclein (a syn) protein. Because there are hereditary forms of Parkinson's disease due to mutations (point or duplication mutations) of a syn in the gene, it is known that alterations in the aggregation or levels of a syn are sufficient to cause neurodegeneration. Based on the preliminary results of co location of a syn in the IBs of patients and animal models for HD, it was hypothesised that a syn is a key mediator in the pathogenesis of HD. The main objective of the proposal is, therefore, to generate and analyse transgenic mice with HD with different gene doses of a syn. 


5 articles published in Journals
1 paper at national conferences
1 paper at international conferences  

José Javier Lucas Lozano 

Date and place of birth: 18th August 1965, San Javier (Murcia).
Current professional situation: CSIC Research Professor Severo Ochoa Centre for Molecular Biology CSIC/UAM.
UAM Cantoblanco Campus, 28049 Madrid and the Networked Biomedical Research Centre for Neurodegenerative Diseases (CiberNed).

1993: Ph.D. in Biological Sciences. Autonomous University of Madrid / Cajal Institute, CSIC.

1989: Degree C.C. Biochemistry and Molecular Biology. Autonomous University of Madrid.


The research career of Dr. José J. Lucas has focused on studying the causes and possible treatment strategies of different central nervous system diseases such as Huntington's disease, Alzheimer's disease, addiction to psychostimulants or pain, at both molecular and cellular level and in vivo through the generation and characterisation of genetically modified animals.

His Ph.D. studies (1990-1993) at the Cajal Institute at the CSIC in Madrid resulted in significant progress on the molecular basis of pain regulation (Oncogene 6: 223-227, 1991 and Neuron 10: 599-611, 1993).

In his postdoctoral sojourn at Columbia University in New York (1994-1997), he discovered important molecular keys underlying addictive disorders. Notable from this period are his studies on serotonin receptor 5 HT1B knockout mice as an animal model for addiction (Mol. Pharmacol. 51:755-763, 1997 and Nature 393: 175-178, 1998). The importance of this work is underlined by having been the subject of a "News & Views" feature in the journal Nature (393: 118-119, 1998).

On his return to Spain, Dr. Lucas's research career has continued at the Severo Ochoa Centre for Molecular Biology in Madrid, which belongs to the CSIC, and at the Autonomous University of Madrid, where he is currently CSIC Research Professor. His research group of is also part of the Networked Biomedical Research Centre for Neurodegenerative Diseases (CiberNed). In the past few years, the research activity by Dr. Lucas has focused on the study of neurodegenerative diseases, especially Huntington's and Alzheimer's.

Dr. Lucas has been a pioneer in generating conditional transgenic mice as animal models of human pathologies. In these models, the pathogenic expression of transgenes can be activated or inactivated at will at various times in the life of the animal. This approach allows research into which aspects of the disease are more likely to be reversed and therefore healed. Dr. Lucas applied this approach for the first time in an animal model for Huntington's disease (Cell 101: 57-66, 2000, an article cited more than 450 times).

The conditional animal model of Alzheimer's disease by overexpression of the kinase GSK-3 (EMBO J. 20: 27-39, 2001, an article cited more than 350 times) has been a key tool for understanding the mechanisms underlying neurodegeneration and cognitive deficits in Alzheimer's disease.

Another important contribution to biomedical research by Dr. Lucas's group focuses on studying the possible role of a malfunction of the ubiquitin proteasome system in Huntington's and other neurodegenerative diseases. (PNAS 106:13986-91, 2009, J. Neurosci. in press, 2010).

In short, the work of Dr. Lucas is reflected in more than 60 publications in indexed international journals including the most prestigious such as Nature, Cell, Neuron, EMBO Journal and PNAS. His works have been cited over 2500 times (an average of more than 40 citations per paper) and have led to several patents.

*All intellectual property rights belong to the author. Reproduction of all or part of the work without permission from the author is prohibited.
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