Paradigm Challenge / Neuroscience

Microglia cells in the brain act as a secret brake to stop the uncontrollable shaking caused by Parkinson's medication.

The Takeaway

Immune cells in the striatum produce a protein called sTREM2 that protects the brain from the side effects of levodopa. Patients with Parkinson's often develop jerky, involuntary movements called dyskinesia after taking their primary medication for several years. These microglia use the TrkB receptor to support circuit plasticity and prevent the nervous system from misfiring during treatment. Most researchers previously viewed these immune cells as villains that drive inflammation and cause further brain damage. This discovery suggests that strengthening these specific immune responses could allow patients to take life-changing medication without the debilitating side effects of movement disorders.

By SeriesFusion Editorial Board · May 8, 2026

Original Paper

Microglial sTREM2 limits dyskinesia and acts on TrkB to support circuit plasticity

Castagnola, C.; Marongiu, R.; Wan, Y.; Torres, E. R. S.; Fan, L.; Jang, M. W.; Cui, Q.; Kim, J.; Ye, P.; Zhu, J.; Panichkina, A.; Fall, A. B.; Norman, K.; Gao, B.; Foxe, N.; Wong, M. Y.; Zhu, D.; Bhagwat, M.; Gong, S.; Orr, A. G.; Lee, F. S.; Surmeier, D. J.; Kaplitt, M. G.; Gan, L.

bioRxiv · 10.64898/2026.05.06.723382

From the abstract

Microglia continuously survey the brain and shape neuronal activity, but their contribution to experience-dependent synaptic plasticity is unclear. Levodopa-induced dyskinesia (LID) is a disabling complication of late-stage Parkinson's disease (PD) that is linked to maladaptive striatal remodeling and is often assumed to reflect detrimental neuroinflammation. Here we identify a dyskinesia-associated microglial gene program in the striatum of PD patients and show that microglia instead act as a p

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