Telomere shortage as model for microglia aging and its implication for neuronal survival
Final Report Abstract
Recent studies indeed have linked telomere dysfunction to various neurological diseases, which indicates the importance of telomere erosion with ageing as a major risk factor in neurodegenerative disorders. As such, telomere length in leukocytes serves as a common predictor for neurological disease and telomere shortening has been observed in patients with dementia and Parkinson’s disease. However, as studies on this subject are controversial, further research is needed to elucidate the effect of telomere shortening on microglia function and its impact for the development of neurodegenerative diseases. We have here evaluated the effects of telomere shortening on microglia in physiology and disease. Our results clearly show that microglia with short telomeres respond differently than their wild type counterparts in the presence of a given neuropathological stimulus. The final outcome of this different response type, however, may depend on whether or not TERC-/- deficiency also leads to the opening of the BBB and a resulting infiltration of peripheral immune cells. This, yet not understood, property of TERC-/- animals makes it very difficult to investigate the function of microglia, as in case of peripheral infiltration it almost is impossible to discriminate the functional contribution of a given cell type in brain pathology.
Publications
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Central nervous system myeloid cells as drug targets: current status and translational challenges. Nat Rev Drug Discov. 2016 Feb;15(2):110-24
Biber K, Möller T, Boddeke E, Prinz M
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Cellular and Molecular Characterization of Microglia: A Unique Immune Cell Population. Front Immunol. 2017 Mar 2;8:198
Sousa C, Biber K, Michelucci A
