NGFN-PLUS
Functional Genomics of Parkinson`s Disease
Coordinator: | Prof. Dr. T. Gasser | |
Institution: | Hertie-Institut für klinische Hirnforschung | |
Homepage: | http://www.hih-tuebingen.de |
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in our ageing society. It is assumed that PD is caused by an interplay of the “environment”, with ageing as the single most important risk factor, and genetic factors. 5% of the patients exhibit a monogenic, inherited form (familiar), 95% develop the disease without evident pattern of inheritance (sporadically). Although the familial forms of the disease account only for a relatively small proportion of all cases, the discovery of the causative genes has identified molecular pathways which are likely to be also critically involved in the etiology of the sporadic forms of the disorder. In families with dominant PD, mutations in the gene for alpha-synuclein or LRRK2, by far the most common form in familial and sporadic cases of PD, are thought to be crucial for the pathogenesis of PD. Whereas mutations in the parkin gene or PINK1 can cause recessive parkinson of early-onset.
Understanding the molecular mechanisms of neurodegenerative diseases is pivotal to develop disease modifying therapeutic strategies. As a consequence, the network “Functional genomics of Parkinson`s Disease” explores all aspects of the disease.
The network is composed of two modules:
The first module (genetics, genomics and proteomics of PD) mainly aims to identify genes of late- as well as early-onset PD, using samples from a large number of patients with sporadic and familial PD. Part of the work is also focused on the search for biomarkers and expertise in neuroimaging complement the approach of the first module.
The second module (molecular pathways to PD in model systems) allows a comprehensive approach to the functional analysis of PD-related pathways. Members of the network have generated diagnostic and manipulatory reagents as well as model systems for practically all established PD genes in a multitude of organisms and cellular systems. This module is able to validate genetic findings and deliver candidate genes to the genetic projects.
All data from gene and protein networks as well as all model systems are integrated to generate a comprehensive model of PD pathogenesis. This model will not only provide all projects with important clues as to where to focus their research, but is also expected to translate directly into practical areas such as the detection and validation of novel drug targets and the identification of suitable patient populations for rapid translation into clinic trials.
Latest results can be found in detail in the descriptions of the subprojects.
Understanding the molecular mechanisms of neurodegenerative diseases is pivotal to develop disease modifying therapeutic strategies. As a consequence, the network “Functional genomics of Parkinson`s Disease” explores all aspects of the disease.
The network is composed of two modules:
The first module (genetics, genomics and proteomics of PD) mainly aims to identify genes of late- as well as early-onset PD, using samples from a large number of patients with sporadic and familial PD. Part of the work is also focused on the search for biomarkers and expertise in neuroimaging complement the approach of the first module.
The second module (molecular pathways to PD in model systems) allows a comprehensive approach to the functional analysis of PD-related pathways. Members of the network have generated diagnostic and manipulatory reagents as well as model systems for practically all established PD genes in a multitude of organisms and cellular systems. This module is able to validate genetic findings and deliver candidate genes to the genetic projects.
All data from gene and protein networks as well as all model systems are integrated to generate a comprehensive model of PD pathogenesis. This model will not only provide all projects with important clues as to where to focus their research, but is also expected to translate directly into practical areas such as the detection and validation of novel drug targets and the identification of suitable patient populations for rapid translation into clinic trials.
Latest results can be found in detail in the descriptions of the subprojects.
- TP1 Scientific Coordinating Office
- TP2 Genomics of Parkinson’s Disease
- TP3 Mutations in recessive Parkinson’s disease genes
- TP4 siRNA-based therapy in models of Parkinson disease
- TP5 Modifier screen in flies overexpressing LRRK2
- TP6 Molecular mechanisms of pathogenic misfolding of α-synuclein
- TP7 Biomarkers of the common Parkinson pathway: Autosomal recessive Parkinson shows alpha-Synuclein induction and synaptic pathology
- TP8 Impact of proteolytic cleavage of alpha-synuclein by calpain in the pathogenesis of Parkinson’s Disease (PD) in a transgenic animal model
- TP10 Mitochondrial stress response in neurodegeneration and aging: OMI and DJ-1 mediated signalling pathways
- TP11 The physiological and pathological function of PINK1, parkin and alpha-synuclein
- TP12 Functional characterization of LRRK2 in mammalian cells and tissues
- TP13 Dopaminergic dysfunction and molecular pathways to selective neurodegeneration: from mouse models to Parkinson disease.
- TP14 Characterization of genetic mouse models for Parkinson´s disease
- TP15 Proteomics platform
- TP16 Bioinformatics platform
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