Research
Other research interests
Role of mutated proteins associated to familial forms of Parkinson’s disease
In the past few years, mutations that cause familial forms of Parkinson’s disease (PD) have been identified in several genes, including alpha-synuclein, parkin, DJ-1, PINK-1 and Dardarin/LRRK2. Exploring how these mutations lead to familial forms of PD should provide important clues to understanding the pathogenesis of the sporadic forms of the disease and allow the development of new genetic models of PD.
Differental susceptibility of dopaminergic terminals versus neuronal cell bodies
Most neuroprotective strategies in experimental PD preserve DA cell bodies in the substantia nigra pars compacta (SNpc) but fail to protect against striatal DA terminals degeneration. As the motor symptoms of PD are caused by the loss of DA terminals in the striatum, preventing the death of DA cell bodies without preventing the degeneration of their axons is unlikely to be a helpful therapeutic strategy. Neurons might have two self-destruction programmes, one for the cell body and a second one for the axon. So, a combination of neuroprotective strategies might be required to obtain optimal clinical benefit.
Molecular links between aging and PD
So far, the most consistent risk factor for developing PD is increasing age. However, the molecular link between aging and neurodegeneration, and whether normal aging is invariably associated with neuronal death, is currently unknown.
Expand PD research beyond nigrostriatal dopaminergic system
Most of the current research in the field of PD is focused on the nigrostriatal dopaminergic system. However, the neurodegenerative process extends well beyond dopaminergic neurons, including the locus coeruleus, raphe, nucleus basalis of Meynert, motor nucleus of vagus, cerebral cortex, olfactory bulb, and autonomic nervous system, which accounts for the increasingly critical role of "non-dopaminergic" symptoms to the quality of life of PD patients. New research lines have to take into account the widespread nature of the PD pathological process.
Develop new tools for the early/pre-symptomatic detection of PD
It is believed that the neurodegenerative process in PD starts many years before the appearance of the first clinical symptoms. In order to apply any potential neuroprotective therapeutic approach to PD patients, the earlier in the disease process that this approch would be applied, the more effective the treatment should be. Therefore, in parallel to studying the molecular mechanisms of neurodegeneration, new tools for the early/pre-symptomatic detection of PD, which are currently lacking, have to be developed. This task requires a multidisciplinary approach involving basic scientists, clinicians, engineers and bioinformaticians.
Develop new methods for the selective targeting of therapeutic molecules
From a therapeutic point of view, it would be important to be able to selectively modulate the molecular mechanisms leading to neurodegeneration in PD in a specific organ or cell type, such as SNpc DA neurons, without adverse effects on other systems. This is especially relevant in the context of chronic processes such as neurodegeneration that would require a sustained neuroprotective treatment. Further research to solve this issue should thus be encouraged.
Identify molecular mechanisms common to other neurodegenerative conditions
Elucidating the mechanisms of neuron cell death in PD should offer important clues to identifying molecular pathways that may be in play in other neurodegenerative disorders. For instance, considerable evidence demonstrates that PD share common clinical and neuropathologic features with Alzheimer’s disease. In addition, some molecular mechanisms leading to cell death in PD have also been described in other neurodegenerative conditions such as Amyotrophic lateral sclerosis of Huntington’s disease. Such overlap may reflect common pathogenic mechanisms for the neurodegeneration encountered within specific vulnerable neuronal populations.
