Microglia, key immune cells of the CNS, maintain brain health but can become dysfunctional and pro-inflammatory with age, harming nearby cells and driving neurodegeneration. Our group studies how microglia regulate brain homeostasis and change with aging and disease.
© Hannah Scheiblich
Normal brain aging and neurodegenerative diseases share key hallmarks, including brain volume loss and cognitive decline, often linked to inflammation. Microglia, the brain’s innate immune cells, are central to these processes. They maintain brain homeostasis by clearing debris, providing neurotrophins, and regulating neuronal activity. However, aging can impair microglial functions, pushing them into a senescent, pro-inflammatory state. This shift compromises their ability to clear cellular debris and support neurons, contributing to chronic inflammation and neurodegeneration. These changes can disrupt memory, neuronal regeneration, and information processing, creating a hazardous environment within the CNS.
Our group focuses on understanding how microglia regulate brain homeostasis and the changes they undergo during aging and neurodegenerative conditions. We emphasize their interactions with neurons and other brain cells. A recent discovery in our lab revealed that microglia form tunneling nanotubes (TNTs), which connect cells and redistribute cytotoxic aggregates to less burdened microglia for degradation. TNTs also transfer healthy mitochondria to stressed neurons, reducing oxidative stress and improving cell survival. This mechanism highlights a critical microglial role in rescuing impaired cells.
However, aging and inflammation can disrupt TNT formation, leading to accumulation of cellular damage and accelerating neurodegenerative disease progression. Our research aims to unravel the mechanisms that regulate TNT formation and their role in maintaining brain health, providing insights into new therapeutic strategies for combating brain aging and neurodegenerative diseases.
Microglia are the brain's adaptable caretakers, shifting from housekeeping to defense. Aging disrupts this balance, driving chronic inflammation and neurodegeneration. Understanding their shifts could unlock new paths to preserving brain health in aging and disease.
© Hannah Scheiblich
The primary goal of our research group is to understand the mechanisms through which microglia regulate brain homeostasis and how these processes are altered during ageing and neurodegenerative diseases. We aim to uncover the cellular and molecular changes that microglia undergo with age, which compromise their ability to maintain a balanced and healthy brain environment. By examining the transition of microglia from their housekeeping role to a pro-inflammatory, adaptive response state, we seek to identify how these shifts contribute to the chronic inflammation associated with age-related neurodegenerative diseases.
A key focus of our research is to investigate how microglia communicate and interact with other brain cells, most importantly, neurons. We aim to understand how microglial dysfunction impacts the overall integrity of brain cell networks and how these interactions may drive the onset and progression of neurodegenerative conditions. Ultimately, our goal is to identify therapeutic strategies to restore microglial function and mitigate the inflammatory processes contributing to age-related brain disorders.
1. Microglia rescue neurons from aggregate-induced neuronal dysfunction and death through tunneling nanotubes. Scheiblich H, Eikens F, Wischhof L, Opitz S, Jüngling K, Cserép C, Schmidt SV, Lambertz J, Bellande T, Pósfai B, Geck C, Spitzer J, Odainic A, Castro-Gomez S, Schwartz S, Boussaad I, Krüger R, Glaab E, Di Monte DA, Bano D, Dénes Á, Latz E, Melki R, Pape HC, Heneka MT. Neuron. 2024. doi: 10.1016/j.neuron.2024.06.029.
2. Microglia jointly degrade fibrillar alpha-synuclein cargo by distribution through tunneling nanotubes. Scheiblich H, Dansokho C, Mercan D, Schmidt SV, Bousset L, Wischhof L, Eikens F, Odainic A, Spitzer J, Griep A, Schwartz S, Bano D, Latz E, Melki R, Heneka MT. Cell. 2021. doi: 10.1016/j.cell.2021.09.007.
3. Microglial NLRP3 Inflammasome Activation upon TLR2 and TLR5 Ligation by Distinct α-Synuclein Assemblies. Scheiblich H, Bousset L, Schwartz S, Griep A, Latz E, Melki R, Heneka MT. J Immunol. 2021. doi: 10.4049/jimmunol.2100035.
4. Characterizing microglial senescence: Tau as a key player. Karabag D, Scheiblich H, Griep A, Santarelli F, Schwartz S, Heneka MT, Ising C. J Neurochem. 2023. doi: 10.1111/jnc.15866.
5. NLRP3 inflammasome activation drives tau pathology. Ising C, Venegas C, Zhang S, Scheiblich H, Schmidt SV, Vieira-Saecker A, Schwartz S, Albasset S, McManus RM, Tejera D, Griep A, Santarelli F, Brosseron F, Opitz S, Stunden J, Merten M, Kayed R, Golenbock DT, Blum D, Latz E, Buée L, Heneka MT. Nature. 2019. doi: 10.1038/s41586-019-1769-z.