Cell and Molecular Neurobiology of Parkinson's Disease (Neurolab)

Basic research in Parkinson's disease
The group has a vast experience in modeling Parkinson's disease. These models recapitulate important aspects of the disease and help to elucidate the molecular basis of this and related neurodegenerative diseases. By investigating previously stablished models of Parkinson's disease we have identified several factors contributing to the progression of the disease, such as oxidative stress, mitochondrial dysfunction, neuroinflammation, genetic mutations and protein aggregation, altered autophagy and toxicity. 
 

Development of neuroprotective strategies
By addressing these issues (e.g. inflammasome and autophagy regulation) we could improve the survival of the dopaminergic neurons in models of Parkinson's disease, opening the field for clinically-oriented approaches.

Brain renin-angiotensin system
In the last few years, we have been particularly interested in the role of the brain renin-angiotensin system in neurodegeneration/neuroprotection of dopaminergic neurons (see Figure 1). Its implication in Parkinson disease via oxidative stress, inflammation and mitochondrial regulation make this system an ideal target for modulation of the disease. Several lines of evidence point to a crucial role of renin-angiotensin system in the progression of Parkinson's disease and other chronic disease, such as metabolic syndrome and COVID19. 

Mutant and misfolded alpha-synuclein protein
Mutant and misfolded alpha-synuclein protein and Lewy bodies are hallmarks of Parkinson's disease. Synuclein aggregation and interaction with other proteins disrupt normal cellular function and lead to cell death.

In vitro generation of dopaminergic neurons
In vitro generation of dopaminergic neurons from neural stem cells or induced pluripotent stem cells (iPs) for research in Parkinson's disease. These cells are useful for cell therapy, as well as modeling the disease and drug discovery. We are investigating the use of stem cell therapy to replace damaged or dying brain cells in models Parkinson's disease. Also, by using these cells, we could alleviate the burden imposed in animal models of the disease, as well as improve currently used strategies for disease modeling and drug discovery for Parkinson.

Dyskinesias
Dyskinesias- Among therapeutic goals, the tackling and management of dyskinesias is another line of research. These involuntary movements appear during the progression of the disease, typically associated to currently used clinical therapies, but the causes of these dyskinesias and how to reduce their appearance is still unclear.

Early markers of Parkinson disease
Early markers of degeneration are absolutely necessary for development of neuroprotective treatments, as the clinical symptoms of the disease appear when about 80% of dopaminergic terminals have already dissapeared.