The Neurodegenerative Diseases Research Group at the Vall d’Hebron Research Institute (Barcelona) was created in January 2006 with the support of the Catalan Institution for Research and Advanced Studies (ICREA) and the European Commission’s Marie Curie Excellence Grants Program. The group is part of the Spanish Network of Excellence on Neurodegenerative Diseases (CIBERNED).
The research conducted in our group is geared toward elucidating the molecular mechanisms of neuron cell death occurring in neurodegenerative disorders, with the aim of finding a cure for this group of disabling, currently incurable, neurological diseases. To this end, our work mostly focus on Parkinson’s disease, a particular neurodegenerative disorder mainly characterized by the degeneration of a specific set of neurons that are anatomically confined to a small region of the brain called substantia nigra pars compacta and that produce the neurotransmitter dopamine.
Elucidating the molecular mechanisms underlying neurodegeneration in Parkinson’s disease should allow the development of new therapeutic strategies aimed at blocking neuronal death in this disorder, as well as elicit important clues to identifying molecular pathways that might be common to other neurodegenerative conditions
Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s dementia and the most common neurodegenerative movement disorder, affecting about 1% of the population above the age of 60. It is estimated that at least 500.000 Europeans are currently affected by this disabling disease, while in the USA alone this number exceeds one million. So far, the most consistent risk factor for developing PD is increasing age. Over the past century, the growth rate of the population aged 60 and over in industrialized countries has far exceeded that of the population as a whole. Thus it can be anticipated that, over the next generation, the proportion of elderly citizens will double and, with this, the number of individuals suffering from PD, as well as the magnitude of the emotional, physical, and financial burden on patients, caregivers, and society related to this disabling illness.
Clinically, classical PD is characterized by resting tremor, slowness of movement, rigidity, and postural instability, all attributed to a dramatic loss of dopamine (DA)-containing neurons in the substantia nigra pars compacta (SNpc), which leads to DA depletion in the striatum. The neurodegenerative process, however, extends well beyond the nigrostriatal dopaminergic system, which accounts for the increasingly critical role of “non-dopaminergic” symptoms to the quality of life of PD patients, especially at later stages of the disease. Thus far, the most potent treatment for PD remains the administration of a precursor of DA, levodopa, which, by replenishing the brain with DA, alleviates almost all PD symptoms. However, during long-term levodopa treatment the therapeutic benefit gradually declines and most patients develop motor and psychiatric side effects, which may be as debilitating as PD itself. Furthermore, levodopa therapy does not halt or retard the progressive death of SNpc DA neurons. Therefore, without undermining the importance of levodopa therapy in PD, there is an urgent need to acquire a deeper understanding of the pathogenesis of PD in order to identify new molecular targets for potential therapeutic intervention.
To this end, we use in vitro and in vivo experimental models of PD-related neurodegeneration, including human-derived samples from patients affected by PD, to unravel the mechanisms of neuronal dysfunction/degeneration in this disease in order to: (i) identify biomarkers for the diagnosis, early detection, patient stratification, disease progression, prognosis or response to treatment, (ii) identify new molecular targets for potential therapeutic intervention, (ii) develop novel therapeutic strategies with disease-modifying potential, (iv) unravel molecular pathways common to other neurodegenerative diseases.
