Abstract

Neurodegenerative diseases are often characterized by mitochondrial dysfunction, leading to increased oxidative stress, energy deficits, and neuronal death. Maintaining mitochondrial health is essential for neuronal function, as these organelles supply the energy needed for synaptic activity and cellular homeostasis. Recent findings from our lab suggest that microglia, the brain’s resident immune cells, can transfer functional mitochondria to neurons through intercellular connections known as tunneling nanotubes. This intercellular exchange has been shown to reduce oxidative stress and promote neuronal survival, highlighting a potential protective mechanism against neurodegeneration. Our research aims to understand the regulation of this mitochondrial transfer and identify the underlying mechanisms that facilitate or impair it. By gaining insights into how microglia support neuronal health through mitochondrial exchange, we hope to uncover novel therapeutic strategies to combat neurodegenerative diseases and enhance neuronal resilience.

Project-related publications

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 (2024) Microglia rescue neurons from aggregate-induced neuronal dysfunction and death through tunneling nanotubes, Neuron, 112:1-20. DOI: 10.1016/j.neuron.2024.06.029

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 MTH (2021) Microglia jointly degrade fibrillar alpha-synuclein cargo by distribution through tunneling nanotubes, Cell, 184(20):5089-5106.e21. DOI: 10.1016/j.cell.2021.09.007

Scheiblich H, Bousset L, Schwartz S, Griep A, Latz E, Melki R, Heneka MTH (2021) Microglial NLRP3 inflammasome activation upon TLR2 and TLR5 ligation by distinct a-synuclein assemblies. J Immunol, 207(8):2143-2154. DOI: 10.4049/jimmunol.2100035