Alzheimer’s disease is a devastating neurodegenerative disorder that affects millions of people worldwide. It causes progressive memory loss, cognitive impairment, and behavioral changes that impair the quality of life of patients and their caregivers. There is currently no cure for Alzheimer’s disease, and existing treatments only offer symptomatic relief.
However, a new study by MIT neuroscientists has revealed a promising new way to reverse Alzheimer’s disease by targeting an overactive enzyme in the brain. The enzyme, called CDK5, is normally involved in regulating neuronal functions, but it can become hyperactive when a protein called P25 accumulates in the brain. P25 is a cleavage product of another protein called P35, which is associated with Alzheimer’s disease and other neurodegenerative disorders.
The researchers found that by blocking CDK5 with a peptide, or a short chain of amino acids, they could prevent P25 from triggering CDK5 hyperactivity and its harmful effects on neurons. The peptide, which was designed to mimic a natural inhibitor of CDK5, was able to cross the blood-brain barrier and reach the affected brain regions.
The results were remarkable: the peptide treatment led to dramatic reductions in neurodegeneration, DNA damage, inflammation, and tau protein accumulation in the brains of mice with Alzheimer’s disease. Moreover, the peptide improved the cognitive and behavioral abilities of the mice, as measured by various tests of memory and learning.
The study, published in the journal Proceedings of the National Academy of Sciences, suggests that CDK5 is a key player in Alzheimer’s disease and a potential therapeutic target. The researchers hope that their findings will pave the way for further development of peptide-based drugs that can reverse Alzheimer’s disease and other forms of dementia.
“This peptide has the ability to enter the brain and in a couple of different models, the peptide shows protective effects against loss of neurons and also appears to be able to rescue some of the behavior deficits,” said Li-Huei Tsai, the senior author of the study and the director of MIT’s Picower Institute for Learning and Memory.
The study also highlights the power of peptides as a novel class of drugs that can modulate specific enzymes and pathways in the brain. Peptides have several advantages over small-molecule drugs, such as higher specificity, lower toxicity, and easier delivery across biological barriers.
“We think that peptides are very promising candidates for drug development because they are more selective and they can be modified to enhance their stability and bioavailability,” said Ping-Chieh Pao, the lead author of the study and a postdoctoral researcher at MIT.
The researchers plan to further optimize their peptide and test it in other animal models of neurodegeneration. They also hope to collaborate with other scientists and clinicians to translate their findings into clinical trials for human patients.
“We are very excited about this discovery and we hope that it will lead to new treatments for Alzheimer’s disease and other forms of dementia,” Tsai said.
