According to WHO reports, dementia has already reached 55 million patients worldwide. The cases increase by over 10 million persons annually, making the medical issue even more worrisome. Those numbers have already affected families, communities, and the economy. Scientists are working to acquire more solutions for the neurological disorder. Aside from studying how someone develops dementia, the research also includes possible preventive measures. Recently, scientists have shared their progress and a new strategy to decrease dementia cases.
Darshan Sapkota, Ph.D., led the study, which has been published in the online journal Brain. They focused their study on amplifying the clearance of waste products from the brains of mice. It is claimed that the process can boost a genetic quirk called a readthrough. According to scientists, a readthrough occurs when the cell’s protein-building machinery stops earlier than it should. For this reason, it results in additional forms of proteins that work less than usual.
“We were studying this very wonky basic science question — ‘How do proteins get made?’ – and we noticed this funny thing. Sometimes the protein-synthesizing machinery blew right through the stop sign at the end and made this extra bit on the end of aquaporin 4. At first, we thought it couldn’t be possibly relevant. But then we looked at the gene sequence, and it was conserved across species. And it had this really striking pattern in the brain: It was only in structures that are important for waste clearance. So that’s when we got excited,” explained senior author Joseph D. Dougherty Ph.D.
As they analyzed the readthrough, the lead authors utilized tools to determine if this protein worked differently than the “normal” one. The longer one was spotted on the endfeet of astrocytes — glial cells that sustain the barrier between the brain and the whole body. The endfeet are vital, as they cover tiny blood vessels in the brain to assist blood flow. They help filter unwanted protein in the brain and flush waste straight into the bloodstream. Therefore, boosting the numbers of long aquaporin 4 is a potential method to extinguish debris and prevent dementia.
The process included screening 2,560 compounds to escalate the readthrough of aquaporin 4. Sapkota discovered apigenin, a dietary flavone found in chamomile, parsley, onions, etc. Also, sulphaquinoxaline, which is a veterinary antibiotic for meat and poultry. Mice were the test subjects that the team treated with apigenin and sulphaquinoxaline, and those mice removed amyloid beta faster than the control group.
Co-author John Cirrito PhD shared, “There’s a lot of data that says reducing amyloid levels by just 20 percent to 25 percent stops amyloid buildup, at least in mice, and the effects we saw were in that ballpark. That tells me this could be a novel approach to treating Alzheimer’s and other neurodegenerative diseases that involve protein aggregation in the brain. There’s nothing that says this process is specific for amyloid beta. It may enhance, say, alpha-synuclein clearance, too, which could benefit people with Parkinson’s Disease.”
The research is still an ongoing process, and the team also shared disclaimers about the method. For instance, sulphaquinoxaline is unsafe for humans to consume. Even though apigenin can be found in dietary supplements, it has yet to be determined how much of it the brain acquires. The team also warned about the apigenin dosage, as it is not advisable to consume too much of it. Scientists have yet to experiment with other drugs that may be effective in increasing the production of long-form aquaporin 4.