Even though synapses in transgenic mice with Alzheimer's may shut down and the mice may lose their memory, upon treatment, they form new synapses and regain their learning and memory abilities.
"For humans, unfortunately, the situation is more problematic because the neurons gradually die in Alzheimer's disease," Bitan said. "That's why we must start treating as early as possible. The good news is that the molecular tweezers appear to have a high safety margin, so they may be suitable for prophylactic treatment starting long before the onset of the disease."
Next, using a radioactive "label," the researchers were able to confirm that the compound had crossed the mouse's bloodbrain barrier and was effective in clearing the brain of amyloid-beta and tau aggregates.
"This work shows that molecular tweezers do a number of things they help to ameliorate multiple pathologic features of Alzheimer's, including amyloid plaques, neurofibrillary tangles and brain inflammation, and our cell culture experiments demonstrated that molecular tweezers block the toxic effect of amyloid-beta on synaptic integrity and communication," Bitan said.
"We call these unique tweezers 'process-specific,' rather than the common protein-specific inhibitors," he added, meaning the compound only attacks the targeted toxic aggregates and not normal body processes. "That's a big deal, because it helps confirm evidence that the molecular tweezers can be used safely, ultimately supporting their development as a therapy for humans."
The next step, Bitan hopes, is to confirm that the tweezers improve memory and not just brain pathology. The researchers say they are working on this question and already have encouraging preliminary data.
|Contact: Mark Wheeler|
University of California - Los Angeles