Exploring long-lived cellular components for neural plasticity and brain aging

Ageing is one of the major risk factors for neurological and psychiatric disorders. However, the biological links between physiological ageing and pathological development are still largely unknown. To tackle this problem, our group has been investigating the role of nuclear structural proteins in the brain, such as lamins and nucleoporins. These structural proteins are known to be part of long-lived protein complexes, but are also targets of aging. We found that these stable structural proteins are critical for organizing cell type-specific epigenome in somatic neural stem cells and maintaining brain function. We also investigated their role in post-mitotic functional neurons, and found that Nup153, one of the nucleoporins, acts as a gatekeeper for neuronal responsiveness by regulating neural plasticity-related gene expression, which is a fundamental process for maintaining neural plasticity.
In addition to long-lived proteins, we have investigated other long-lived cellular components and found that some of RNAs that do not turn over in the mouse brain for 2 years. These extremely long-lived RNAs (LL-RNAs) are retained in the nucleus in a cell type–specific manner. Perturbation experiments revealed that one of the LL-RNAs is required for heterochromatin maintenance and quiescent neural stem cell reactivation, suggesting their functional importance in maintaining somatic stem cell function.

The SCALE lunch seminar will take place in a hybrid form. All interested are invited to attend in person at the lecture hall of the MPI-BP with coffee and a light lunch in the atrium afterwards. At the same time, the lecture will also be streamed online via zoom. The zoom link will be sent by e-mail to the SCALE mailing list. To subscribe to the mailing list, please send an e-mail to scale-office@uni-frankfurt.de.