Scientists have long been racking their brains to crack the mechanism behind Alzheimer’s disease progression.
They may have finally found a crucial clue. A research team from Heidelberg University in Germany recently uncovered a hidden “switch” that acts like a death trigger for brain cells and plays a key role in cognitive decline.
The study also highlighted a new, experimental drug that could block the process, opening up possibilities for more effective treatments in the future.
With over 7 million people over 65 battling the degenerative disease — and the number expected to almost double by 2050 — new treatments are constantly being explored that tackle the toxic proteins that accumulate in the brain.
Researchers from Heidelberg and Shandong University in China used a mouse model of Alzheimer’s to examine a molecular process in the brain involving two previously studied proteins: the NMDA receptor and the TRPM4 ion channel.
Both are essential components: NMDA receptors help maintain cognitive function, while TRPM4 is a membrane protein that affects immune cell function and is linked to neurodegenerative disorders.
When TRPM4 interacts with the receptors outside synapses where neurons connect and communicate, the result is a toxic interaction that researchers describe as a “death complex,” damaging and killing nerve cells.
The study found that this neurotoxic pairing appeared at much higher levels in the Alzheimer’s mice compared to the healthy ones.
The same team had previously discovered the novel pharmaceutical compound FP802, a neuroprotective drug that prevents neurons from dying.
They used this drug to block the interaction between the two proteins and successfully break the deadly complex apart, which slowed the progression of the degenerative disease.
The effects of FP802 didn’t stop there.
The team noted that the compound limited or entirely prevented many of the typical cellular changes from Alzheimer’s, including loss of synapses and damage to mitochondria.
Cognitive abilities that are often affected, such as learning and memory, remained largely intact, and the hallmark amyloid beta deposits were significantly reduced.
According to the researchers, this treatment notably differs from traditional methods.
“Instead of targeting the formation or removal of amyloid from the brain, we are blocking a downstream cellular mechanism… that can cause the death of nerve cells and promotes the formation of amyloid deposits,” study lead Dr. Hilmar Bading of Heidelberg said in a statement.
The team also hopes the treatment can be used for ALS, as the NMDAR/TRPM4 interaction also plays a role in that neurodegenerative disorder.
While this new treatment seems promising, real-world use is still a ways off, as “comprehensive pharmacological development, toxicological experiments and clinical studies are needed to realize a possible application in humans,” according to Bading.
