Michael Heneka Laboratory

Tunneling nanotubes

Project details


Misfolded α-synuclein(α-syn) accumulations and microglial activation represent key pathological hallmarks of synucleinopathies. Even though misfolded α-syn aggregates are first found in neurons evidence suggests that spreading of pathology will expose these proteins to surrounding microglia. Microglia are responsible for the clearance of these aggregated cytotoxic protein accumulations from the brain and represent the main drivers of inflammatory processes within the CNS. Once activated, microglia initiate a range of inflammatory responses including the release of immune mediators which, once chronically present, collectively contribute to neuronal dysfunction and degeneration. They also initiate response mechanisms for phagocytic clearance of the respective protein aggregates.


In this project, we aim to characterize the detailed mechanisms on how microglia deal with the presence of aggregated α-syn accumulations. To address this question, we study the phagocytosis and degradation of aggregated α-syn by microglia as well as signal transduction pathways that are modulated by α-syn aggregates. We focus on how α-syn alter microglia function and how this might impact microglial protein clearance dynamics. Using pharmacological and genetic manipulation tools we investigate the impact of specific targets/pathways on microglia function. In an intercellular approach, we study possible rescue abilities by which microglia relief microglia and/or neurons from an α-syn overload in order to preserve them from dysfunction and degeneration.

Project-related publications

Microglia jointly degrade fibrillar alpha-synuclein cargo by distribution through tunneling nanotubes

Hannah Scheiblich, Cira Dansokho, Dilek Mercan, Susanne V Schmidt, Luc Bousset, Lena Wischhof, Frederik Eikens, Alexandru Odainic, Jasper Spitzer, Angelika Griep, Stephanie Schwartz, Daniele Bano, Eicke Latz, Ronald Melki, Michael T Heneka

Microglial NLRP3 Inflammasome Activation upon TLR2 and TLR5 Ligation by Distinct α-Synuclein Assemblies

Hannah Scheiblich, Luc Bousset, Stephanie Schwartz, Angelika Griep, Eicke Latz, Ronald Melki, Michael T Heneka

Project-related funding

Gemeinnützige Hertie Stiftung

Gemeinnützige Hertie Stiftung

Project-related scientists

Michael Heneka Lab
Michael Heneka Lab

Other Projects