Abstract Body

The intraneuronal or extracellular accumulation of neurotoxic beta-sheet structured amyloids represent key pathological hallmarks of several neurodegenerative disease. While the brain has been considered an immune-privileged organ, increasing evidence suggests that innate immune cells are intimately involved in disease evolution and progression.

Microglia play a pivotal role for this innate immune response and are activated by binding of protein aggregates to pattern recognition receptors. This binding may activate pathways that are involved in phagocytosis and degradation. On the other hand, immune activation of microglia may lead to the release of inflammatory mediators and distracts microglia from their physiological functions and tasks. Microglial distribution of neurotoxic beta-sheet structured cargo may help stressed cells to cope with the inflammatory activation and contribute to the overall successful clearance. Importantly, disease causing mutations and risk polymorphisms for neurodegenerative disease such as Parkinson’s disease and Alzheimer’s disease are being tested for the potential to influence cargo distribution through tunneling nanotubes. Likewise, immune cells help each other by sharing intact mitochondria in order to cover the increased energy demand during an inflammatory challenge. The capability of microglia providing such help to neighboring cells may be key to prevent neurodegeneration.