Christina Ising

Alzheimer’s disease is the most common form of dementia and as a tauopathy, it is characterized by intraneuronal accumulation of the tau protein. Another important hallmark of tauopathies is chronic neuroinflammation. Hence, microglia play an important, but incompletely understood role in these diseases. Upon treatment with specific stimuli, including but not limited to tau, microglia can activate a defense mechanism called the NLRP3 inflammasome. This can ultimately lead to the execution of pyroptosis, a lytic, programmed cell death creating a pro-inflammatory environment and releasing factors that potentially affect other cells including neurons in the brain.

In her postdoc time, Dr. Ising has already shown that NLRP3 inflammasome-dependent release of the pro-inflammatory factor IL-1β from microglia leads to an activation of tau kinases and inhibition of one of the major tau phosphatases via downstream signaling initiated in neurons. In addition, she showed that the tau protein itself can induce NLRP3 inflammasome activation in microglia (Ising et al., Nature 2019). Present work of the Ising lab focuses on mechanisms in pyroptosis execution and other factors released in this process as well as on potential new players in the NLRP3 inflammasome pathway.

However, microglia are also able to go into senescence, a well-known hallmark of aging. Senescence is a cellular state characterized by irreversible cell cycle arrest, metabolic dysfunction and secretion of a senescence-associated secretory profile (SASP), that can also modulate the microenvironment in the brain and affect neighboring cells. The Ising lab showed that the tau protein is also able to induce microglial senescence (Karabag et al., J Neurochem 2023). Since the composition of the SASP and other senescence features greatly depend on cell type and senescence inducer, they now continue to study underlying mechanisms, related SASP factors and their effect on neurons and other bystander cells.