The group works on two main lines of research, whose objectives are summarized below.

a.Mechanisms of Neurodegeneration

The group investigates the cellular and molecular mechanisms underlying neurodegenerative processes, with special emphasis on analyzing molecules that could serve as potential therapeutic targets. To this end, functional genetic analysis is performed on molecules in which mutations associated with familial cases of Parkinson’s disease (PD) have been mapped, such as alpha-synuclein. The possible normal function of these molecules and their relationship with neurodegeneration are studied using genetically modified mouse strains (transgenics, null mutants, etc.). Animal models are used for:

1. Functional analysis at the cellular and system levels,
2. Studying the interaction of genetic alterations with toxic disease models,
3. Genetic screening of factors that interact with known molecules,
4. Expression profiling (genomic analysis) using DNA chips to identify molecules whose expression is coordinately altered in different genetic model situations, followed by a phylogenetic comparative analysis of the identified molecules and their interrelations in the context of the pathology,
5. Identification of mouse genes for genetic alteration (production of null mutants, transgenics).

In this context, the group is part of CIBER in Neurodegenerative Diseases, the virtual center funded by the Carlos III Health Institute for cooperative and translational research in neurodegeneration in our country.

b.Cell Therapy

The group studies stem cells as a potential therapy to replace lost neurons, with particular relevance to molecules that may modulate the proliferation and/or differentiation of these stem cells toward a dopaminergic phenotype, as well as signals that induce self-renewing division of neural stem cells. In this line, the following are conducted:

1. Characterization of niche-derived signals and intracellular signaling pathways involved in maintaining multipotency in neural stem cells,
2. Studies of soluble niche factors that may modulate neural stem cell responses and could be implemented to improve ex vivo cultures of these cells,
3. Characterization of niche-derived signals and intracellular signaling pathways involved in neurogenesis, especially dopaminergic, from neural and embryonic stem cells,
4. Study of the genetic stability of neural stem cell cultures over time in vitro,
5. Understanding uncontrolled expansion processes of neural stem cells and their relation to tumor formation,
6. Generation and analysis of induced pluripotent stem cells from skin biopsies of Parkinson’s disease patients and their potential for dopaminergic neurogenesis.

The research group is a member of the National Network of Cell Therapy, funded by the Carlos III Health Institute to promote therapeutic strategies based on stem cell use in degenerative diseases and tissue engineering.

In the context of cell therapy, the research team has developed a new procedure that allows inducing self-renewal of stem cells through the novel use of PEDF. The PEDF factor is a complex protein previously identified in the state of the art as a factor with multiple uses and applications in the body, but the research team has identified a new use of PEDF as a self-renewal factor both in vivo and in vitro. This new use of PEDF has been protected by a patent application to improve the efficiency and therapeutic potential of current regenerative medicine treatments, also facilitating the development of new drugs and new treatments based on cell therapy. It is noteworthy that various companies and institutions have expressed interest in applying these research results in diverse areas of regenerative medicine, such as treatments for cardiovascular injuries and diseases.