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An integrated approach towards understanding the pathogenesis of neurodegeneration (NEUROBRAINNET)

Research project P7/16 (Research action P7)

Persons :

Description :

The proposed network – NEUROBRAINNET – brings together researchers specialized in clinical neurology, neuropathology, genetics and genomics, cell biology and model organisms, protein modelling and translational research, who are active in the domain of neurodegenerative brain diseases. The network will focus its research activities on neurodegenerative diseases of the central nervous system (CNS) such as Alzheimer disease, frontotemporal lobar degeneration, dementia with Lewy bodies, Parkinson disease and related spectrum disorders including amyotrophic lateral sclerosis.

The network project aims to gain a better understanding of the process of neurodegeneration that lead to these major diseases. These devastating diseases, of which numbers increase with the progressing aging process in our society, have a tremendous impact on the quality of life of the patients as well as their caretakers and lead, often after a long and debilitating course, ultimately to death. Although these diseases have major socio-economical consequences worldwide, no efficient cures are yet available.

The network consists of 5 partner groups that together represent leading teams active in neurodegenerative brain research in Belgium. The network also liaisons with four international leading teams of the Netherlands (Rotterdam), Germany (Aachen and Kiel) and France (Lille). Several of these groups have received worldwide recognition for their work, as exemplified by major research prizes, publications in top-tier journals, international funding (e.g. EU, USA) and participations in international networks. Furthermore, some of the co-principal investigators in the network partner groups are either emerging young leaders or new teams. Some of these investigators recently returned to Belgium after prolonged stays abroad to start their research own groups/teams in Belgium. Thus, next to the ambitious scientific objectives of the network, we also aim at integrating young promising scientists into a major and dedicated scientific network, providing them access to major research infrastructure present in the established groups of the principal investigators, creating and fostering scientific interaction and training, and in doing so, increasing the visibility of major research efforts in Belgium aiming at increasing our understanding of these debilitating diseases.
The partners aim at clarifying a series of fundamental scientific questions related to the pathophysiological processes underlying these diseases. More specifically, they aim at identifying biological pathways that are linked to these diseases, by identifying novel genes and genetic risk factors, by identifying modifiers of genetic function by genetic screens, by analyzing the functional networks in which the proteins encoded by these genes are operating, and ultimately, by providing novel avenues for early diagnosis, prognosis, prevention and treatment.

While neurodegenerative brain diseases represent a heterogeneous mix of pathological entities, over the last years it has become obvious that several recurrent themes appear in all these entities. All compromise the nervous system, are usually characterized by a later age of onset, present with synaptic dysfunction, and many are characterized by biochemical abnormalities, such as abnormal cellular “inclusions” or accumulation of peptides. From a mechanistic point of view, neuronal function is jeopardized by axonal transport problems, mitochondrial dysfunction, nerve conductance or neurotransmission deficiencies, or increased vulnerability to cellular stress resulting in apoptosis. Moreover, technological approaches in the different disease domains overlap considerably, and for these two reasons – i.e. conceptually at the scientific level and practically at the experimental level – we brought together these teams in an integrated network.

While the scientific interaction is usually more difficult to steer in a top down approach, the technological interaction is an almost natural way of organizing different groups in a network, and we therefore defined 5 workpackages covering the different steps of the research workplan to be developed over different areas.

These workpackages are:

Clinical neurology and human pathology:
Genetics, genomics and functional genomics
Cell Biology and model organisms
Protein and proteostatic network modelling
Translational research

In each workpackage, several research teams are involved with specific additive or complementary expertise in defined areas. We expect that interactions between these groups will provide a significant and critical mass needed to address the main research questions of the project.
This proposed IAP network – NEUROBRAINNET – project is a competitive renewal for continuation of the currently active network P6/43 – NEURONET – that was successfully reviewed in the international ex poste evaluation organized by BELSPO. Therefore, we propose to continue our study of the pathogenesis of neurodegeneration in a multidisciplinary and interdisciplinary approach though with a complete focus on neurodegenerative brain disease as suggested by the referees. Further, taking into account the expertise of the PIs and their co-PIs, as well as the scientific output, interactions and achievements obtained in the previous network project, we have condensed the project into 5 major work packages. With our integrated team of clinical and basic researchers with expertise in clinical neurology and pathology, genetics, genomics and functional genomics, cell biology and animal models, structural biology and bioinformatics, we will further increase our knowledge of the etiology of neurodegenerative brain diseases trying to bridge the gap with the clinic via translational research and medicine providing novel avenues for diagnosis, prevention and treatment.

In conclusion, this network proposes a major research effort into the understanding of neurodegenerative brain diseases by bringing together a number of excellent research groups in Belgium and Europe, creating a virtual research department providing an international competitive critical mass in this research area.

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