Functional Genomics of Parkinson`s Disease

Coordinator:    Prof. Dr. T. Gasser
Institution: Hertie-Institut für klinische Hirnforschung
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.
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