A group of scientists led by Professor Hilmar Bading at Heidelberg University discovered a key step that makes Alzheimer’s disease get worse. Working with researchers from Shandong University in China, they used mice that mimic the disease. They found that a bad protein partnership makes brain cells die, which hurts memory and thinking.
How the Bad Protein Pair Works
The two proteins are the NMDA receptor and the TRPM4 ion channel. NMDA receptors help brain cells talk to each other and are normally good for keeping neurons alive. When they sit at the connections (synapses), they protect memory.
But when the TRPM4 channel attaches to NMDA receptors outside the synapse, the pair changes the receptor’s behavior. This creates a "death complex" that damages and kills neurons.
Drug Stops the Toxic Connection
The researchers used a compound called FP802, which they call a "TwinF Interface Inhibitor." FP802 fits into the spot where the two proteins meet, called the TwinF interface, and blocks them from sticking together.
In the mouse experiments, FP802 broke apart the harmful NMDA‑TRPM4 complex.
Benefits Seen in Treated Mice
Mice that received FP802 showed a much slower disease course. Their brains lost fewer synapses, and the tiny power plants inside cells (mitochondria) stayed healthier.
Most importantly, the mice kept their learning and memory abilities. They also had far less buildup of beta‑amyloid, a protein that usually piles up in Alzheimer’s brains.
Why This Is Different From Other Treatments
Most Alzheimer’s drugs try to clear or stop the formation of amyloid plaques. This new approach does not target amyloid directly. Instead, it blocks a later step—the toxic NMDA‑TRPM4 complex—that can cause cell death and even encourage more amyloid to form.
Earlier work showed that FP802 also protects nerve cells in a mouse model of ALS, another disease that involves the same protein pair.
What Comes Next?
The team thinks this inhibitor could help slow many brain‑degeneration diseases, but it is still far from being used in people. More work is needed to test safety, dosage, and effectiveness in humans.
Scientists are now working with the company FundaMental Pharma to improve FP802 for possible future medicines.
Funding and Publication
The study was supported by the German Research Foundation, the European Research Council, the former German Ministry of Education and Research, the National Natural Science Foundation of China, and the province of Shandong. Results were published in the journal Molecular Psychiatry.