How about a real Alzheimer’s breakthrough?
Dr. Li Huei Tsai (director of MIT’s Picower Institute of Learning and Memory) and his group have found a way to reverse brain neurodegeneration caused by Alzheimer’s. They do so by interfering with an enzyme (using a peptide) that becomes overactive when Alzheimer’s is around.
The enzyme is CDK5, which is necessary for many neuronal processes (in particular learning and the formation of memories. The team hopes this will lead to treatment for Alzheimer’s patients who manifest dementia due to CDK5 overactivation. The peptide does not interfere with CDK1, which Is structurally similar, and another essential enzyme.
Without overactivity, CDK5 is regulation by P35 or P39 (both coactivators). But, when P35 is cleaved by calpain (forming the truncated activator P25), the P25 binds to CDK5 (it phosphorylates), leading to overactivation and altered substrate specificity. So, the trick is to preclude calpain cleavage, which the group accomplished by using a 12 amino acid long CDK5 derived peptide.
Drug companies tried to do the same thing with small molecule drugs, but found those choices interfered with other essential enzymes. So, the use of a peptide was a welcome improvement.
Using laboratory conditions with the neurons growing in culture, Tsai’s team found the peptide effected a moderate reduction in CDK5 activity. When they tried the same experiment in mice, they noticed many benefits- reductions in DNA damage, neural inflammation, and neuronal loss. They also found changes in gene expression (increasing 20 genes activated by MEF2).
Finally, a promising step in Alzheimer’s treatment.
I am so excited about the breakthrough of Alzheimer’s and dementia disease. My hope is that both will be a thing of the past by the time my grandchildren and great grands get older.
Love that aspiration, Martha!
I love stories like this. As a supporter of Parkinson’s research, I was thrilled to see a breakthrough in how doctors can detect PD before the onset of symptoms. Right now, it’s a spinal tap, but soon enough, it will be a blood test, and then who knows what. So many new medications can be developed from this discovery.
I also used to work for a childhood cancer charity and see donations at work. No matter how big or small, supporting the researchers will ultimately lead to better treatments and cures. Thanks for sharing!
Yes, I know all about that childhood cancer charity for whom you were employed. My daughter was also involved (they were next-door neighbors).