Subject
Which is the mechanism involved in neuronal death that leads to neurodegenerative diseases such as Parkinson ‘s Disease, Multiple Sclerosis or Huntington ‘s Disease? Which is the role of inflammation regarding these processes? 
Taking into account the possibility to generate human reprogrammed stem cells from tissues such as skin, and differentiate these reprogrammed cells to neurons, is it possible to develop a treatment involving regenerative medicine for Parkinson Disease? What is the impact of inflammation on the efficacy of these cellular therapies on the brain?

Approach
We use neuronal models based on reprogrammed stem cells, rodent animal models and Fruit Fly models (Drosophila melanogaster).  Likewise, we develop and use viral vectors for gene transfer, and a wide range of techniques including functional genomics, molecular biology, cellular biology, biochemistry, histochemistry and image analysis. 

Advances
Our Laboratory had been pioneer in establishing that inflammation can cause neuronal death on the substantia nigra, the brain region which is mainly affected by Parkinson ‘s Disease, and causes motor symptoms. Additionally, we had determined that chronic inflammation can lead to demyelination of certain brain regions which are relevant to Multiple Sclerosis. 
Basic research which could be relevant in the future to cause clinical impact, relies on the availability of models in order to study the disease pathology. We have developed 5 animal models of neurodegeneration and motor symptoms in which rats are injected with Adenoviral vectors overexpressing pro-inflammatory cytokines such as Interleukin-1 and Tumor Necrosis Factor Alpha into the substantia nigra. Likewise, we developed 2 animal models for brain demyelination, aiming to study Multiple Sclerosis, one of those for the Primary Progressive type. In these models, we have demonstrated that peripheral chronic inflammation exacerbates neurodegeneration and symptoms in these diseases. Finally, we ‘ve established a method to study Benign Infantile Epilepsy based on neurons derived from human reprogrammed stem cells. 
We have identified the PMCA1 gene as a candidate to mediate the dysfunction of dopaminergic neurons affected in Parkinson ‘s Disease. This candidate gene is a molecule that pumps calcium out of the cells and its downregulation causes an increase on intracellular calcium which leads to neuronal dysfunction. Its identification was based on a gene expression profiling by microarray screening on animal models in which neuroinflammation causes neurodegeneration and motor symptoms. 
We have also observed that inflammation can affect the process that leads the conversion of reprogrammed stem cells into neurons. These neurons are being transplanted into patients affected with Parkinson Disease in Japan, and therefore, our approach states the cornerstone for anti-inflammatory treatments which can improve the outcome of cellular transplants.