MIT Scientists Unlock A Major Breakthrough In Battle To Reverse Alzheimer's Disease

Scientists at MIT have discovered a new way to reverse the effects of Alzheimer's disease. The new discovery shows "dramatic reductions" in neurodegeneration.

The researchers used a peptide or string of amino acids. The researchers were able to interfere with an enzyme that is typically overactive in the brains of people with the disease. The chemical compounds blocked the hyperactive version of an enzyme called CDK5 and the researchers found dramatic reductions in neurodegeneration and DNA damage in the brain.

The researchers conducted these tests on mice and they revealed significant and promising results.

Author Li-Huei Tsai, director of MIT's Picower Institute for Learning and Memory, told New York Post, "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 behavioural deficits."

With further testing, the researchers hope that the peptide could eventually be used as a treatment for patients with Alzheimer's disease and other forms of dementia that have CDK5 overactivation. The peptide does not interfere with CDK1, an essential enzyme that is structurally similar to CDK5, and it is similar in size to other peptide drugs that are used in clinical applications, according to a report released by MIT.

It further added, "CDK5 is activated by a smaller protein that it interacts with, known as P35. When P35 binds to CDK5, the enzyme's structure changes, allowing it to phosphorylate - add a phosphate molecule to - its targets. However, in Alzheimer's and other neurodegenerative diseases, P35 is cleaved into a smaller protein called P25, which can also bind to CDK5 but has a longer half-life than P35."

When bound to P25, CDK5 becomes more active in cells. P25 also allows CDK5 to phosphorylate molecules other than its usual targets, including the Tau protein. Hyperphosphorylated Tau proteins form the neurofibrillary tangles that are one of the characteristic features of Alzheimer's disease.

Pharmaceutical companies have tried to target P25 with small-molecule drugs, but these drugs tend to cause side effects because they also interfere with other cyclin-dependent kinases, so none of them has been tested in patients.

When the researchers tested the peptide in a mouse model of Alzheimer's disease that has hyperactive CDK5, they saw a myriad of beneficial effects, including reductions in DNA damage, neural inflammation, and neuron loss. These effects were much more pronounced in mouse studies than in tests in cultured cells.

Not just that, the researchers said that peptide treatment also produced dramatic improvements in a different mouse model of Alzheimer's.

The researchers also analyzed the changes in gene expression that occur in mouse neurons following treatment with the peptide.

The research was funded by the National Institutes of Health.