Clinician Scientist-Programm OrganAge 2021

Thema: "The role of the novel stress-responsive gene mcp-1/GDPGP1 in aging and disease"

Zusammenfassung:
In contrast to most other cell types, mature central nervous system (CNS) neurons are highly vulnerable to cellular stress, show low potential for regeneration and cannot be replaced when lost. Understanding the cellular mechanisms that regulate neuronal stress response and cell death is fundamental for the development of novel therapies, urgently needed for the treatment of neurological disorders. Using a combination of transcriptomic profiling and functional assays in primary mouse neurons and the model organism Caenorhabditis elegans, we have recently identified novel stress-responsive genes in neurons. In particular, the evolutionarily conserved gene mcp-1/GDPGP1 appears to have a functional relevance in neuronal stress response by conferring stress resistance to injured cells. This research proposal aims at characterizing the role of mcp-1/GDPGP1 during aging by investigating its expression in the aged nervous system of C. elegans and mice. By creating a murine mcp-1/GDPGP1 knockout model, its functional relevance in age- and disease-dependent neurodegeneration will be studied. Furthermore, this research proposal aims at identifying upstream regulators of mcp-1/GDPGP1 that mediate its transcriptional down-regulation following cell injury.