The monocytic and microglial transcriptome profile in Parkinson disease

• Applicant: Dr. Johannes Schlachetzki
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Molecular and Cellular Neurology and Neuropathology
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 274210460

Parkinson disease (PD) is the most prevalent movement disorder. Besides the degeneration of dopaminergic neurons in the substantia nigra and the presence of intraneuronal inclusions termed Lewy bodies with alpha-synuclein as the major proteinaceous component, there is evidence for increased microglial activation and elevated pro-inflammatory cytokine levels with the central nervous system in PD. However, whether there is also a peripheral inflammatory component in PD is unclear. Aim of this study is to unravel a potential link between monocytic/microglial mediated inflammatory processes and neurodegeneration. To this end, the transcriptome profile of human monocytes isolated from PD patients will be determined, human microglia as well from monocytes/microglia derived from a transgenic mouse model of PD. Changes in gene expression of monocytes of microglial in the context of PD will be analyzed by RNA expression profiling. The mechanistic basis for identified transcriptional alterations will be addressed using Chromatin-Immunoprecipitation and DNA-sequencing (ChIP-Seq). The following hypotheses will be addressed: 1) Resting and activated monocytes from PD patients show a distinct transcriptional profile; 2) Parallel analysis of monocytic and microglial transcriptome in a transgenic PD mouse model will decipher a distinct transcriptome signature; 3) Monocytic-microglial crosstalk reveals distinct alterations in the transcriptome profile. Deciphering the distinct monocytic/microglial transcriptome signature in the context of PD may be of high significance since it may lead to the development of biomarkers and to the identification of new therapeutical targets.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Christopher K. Glass