Researchers have identified a harmful protein interaction that acts as a “death trigger” for brain cells in Alzheimer’s disease and demonstrated a way to block it in mice. The findings, published in Molecular Psychiatry, point to new therapeutic possibilities for the neurodegenerative condition.

A team led by Professor Hilmar Bading at Heidelberg University, working with researchers from Shandong University in China, found that the toxic interaction involves two proteins: the NMDA receptor and the TRPM4 ion channel. NMDA receptors normally support neuron survival and cognitive function when operating within synapses. However, when TRPM4 interacts with NMDA receptors outside synapses, the proteins form what researchers describe as a “death complex” that damages and kills nerve cells.

The study found significantly higher levels of this neurotoxic complex in Alzheimer’s mouse models compared to healthy animals. To target this mechanism, researchers used FP802, a compound previously developed by Professor Bading’s team. The molecule binds to the interface where the two proteins connect, preventing their interaction and breaking apart the toxic complex.

Mice treated with FP802 showed markedly slower disease progression, with reduced synapse loss, less mitochondrial damage, and largely preserved learning and memory abilities. Researchers also observed a significant reduction in beta-amyloid accumulation, a hallmark of Alzheimer’s.

Professor Bading noted that this approach differs from traditional strategies by targeting a downstream cellular mechanism rather than amyloid formation or removal. Previous research showed FP802 also provides neuroprotective effects in amyotrophic lateral sclerosis models.

The researchers cautioned that clinical application remains distant, with comprehensive pharmacological development and clinical trials still required.

Source: Science Daily / Heidelberg University (Molecular Psychiatry, 2026)