Wir überwinden Grenzen

Important signaling pathway in brain aging identified / Novel drug used to reverse age-related changes in mice / Publication in Nature

A groundbreaking study published in the journal Nature on August 2, 2023, provides new insights into the aging processes in the brain and possible approaches to combat age-related neurodegenerative diseases. The research team led by Prof. Dr. Andrea Ablasser from the École Polytechnique Fédérale de Lausanne (EPFL), Switzerland, conducted the study in collaboration with scientists from the Faculty of Medicine - University of Freiburg.

Novel drug reverses age-related changes
The researchers from the Institute of Neuropathology at the Medical Center - University of Freiburg, together with their Swiss colleagues, showed that the cGAS-STING signaling pathway, which mediates the immune response to DNA, can be a decisive factor in chronic immune cell activation and nerve cell loss and functional decline in old age in mice. "After using a previously developed, novel drug to block STING, the age-related cellular changes were reversed," explains study co-author Dr. Marius Schwabenland, scientist at the Institute of Neuropathology at the Medical Center - University of Freiburg and fellow in the IMM-PACT Clinician Scientist Program of the Faculty of Medicine - University of Freiburg. "Parallel to this, there was an improvement in brain function, such as improved learning and memory."

Conversely, the researchers were able to amplify the cGAS-STING signaling pathway in mice by means of a genetic modification in microglial cells, the scavenger cells in the brain. This amplification alone caused the premature onset of age-related cellular changes and cognitive decline.

Potential for stopping neurodegenerative processes in old age
Prof. Dr. Marco Prinz, Medical Director of the Institute of Neuropathology at the Medical Center - University of Freiburg and also co-author of the study, emphasizes the importance of these results: "The research results indicate that the targeted blockade of the cGAS-STING pathway could be a promising approach for stopping neurodegenerative processes in old age. Nevertheless, further studies need to be conducted to understand the full potential of these findings." The study was carried out as part of the Collaborative Research Center / Transregio 167 "Development, function and potential of myeloid cells in the central nervous system" (NeuroMac), of which Prinz is the spokesperson.

"This study is a great sign of the international research strength of the Medical Center of Freiburg," said Prof. Dr. Lutz Hein, Dean of the Faculty of Medicine - University of Freiburg and member of the Board of Directors of the Medical Center of Freiburg. "It confirms that comprehensive support for young, talented scientists is the right way forward."

Caption: 3D representation of two microglial cells (pink). Microglial cells in mice with cGAS overactivation (right) show an altered, activated morphology compared to mice without mutation (left), which leads to nerve cell atrophy. The cell nuclei are shown in blue.
Image source: Medical Center - University of Freiburg / Marius Schwabenland

Original title of the study: cGAS/STING drives ageing-related inflammation and neurodegeneration
DOI:https://doi.org/10.1038/s41586-023-06373-1
Link to study: cGAS-STING drives ageing-related inflammation and neurodegeneration | Nature