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New protein target may reverse memory loss in Alzheimer’s

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Scientists believe they are getting closer to reversing memory loss in Alzheimer’s disease by targeting an enzyme known as HDAC2. Researchers at the Massachusetts Institute of Technology (MIT), in the U.S. believe that it is possible to reverse memory loss in Alzheimer’s disease with drugs that can stop HDAC2 from interfering with key memory-forming processes.

Scientists previously attempted targeting HDAC2 to reverse memory loss, but the results weren’t acceptable because the drugs produced toxic side effects by disrupting other tasks of the enzyme.

In this new study the researchers discovered that by blocking sp3 – a molecule that binds to HDAC2, it is possible to prevent them both from interrupting communication between brain cells.

Lead author of the study is Li-Huei Tsai, Director of MIT’s Picower Institute for Learning.

“If we can remove the blockade by inhibiting HDAC2 activity or reducing HDAC2 levels, then we can restore expression of all these genes necessary for learning and memory.”

Alzheimer’s is the most common form of dementia, affecting around 850,000 people in the UK. [Read more ]

This rapidly progressing neuro degenerative disease gradually destroys one’s ability to remember, think, and make decisions.

At its end stage, people lose the capability to carry on a conversation and to perform simple everyday tasks.

It is not known what causes Alzheimer’s, but scientists believe it could be due to various factors that affect different people in different ways.

The new research deals with blocking a biological process called synaptic plasticity. This process is thought to be crucial for memory and learning.

memory loss
Neurons in the brains are interconnected by connections known as synapses. These synapses enable the transmission of information from one neuron to another (Image: YouTube screenshot)

By studying synapses – junctions between brain cells – scientists found out that they are superficial and not fixed as the soldered joints seen in electronic circuits.

For over a decade, Prof. Tsai has been researching HDACs’ role in memory loss. In a 2007 study on mice, she found that blocking HDAC activity in these rodents could reverse memory loss. Around a dozen types of HDACs are found in humans.

These enzymes alter proteins called histones. These proteins help transform DNA structure and package them into a form called chromatin.

The HDAC’s effect is to compact chromatin, which, in turn, decreases some gene expressions in the DNA.

After further research, Prof. Tsai discovered that in humans, a specific HDAC known as HDAC2 inhibited some genes that are crucial for memory. She also found that Alzheimer’s patients and mouse models of Alzheimer’s disease had higher levels of this enzyme.

Researchers already tested compounds that block HDAC2, but most of these compounds have side effects. For example, these compounds impede HDAC1, which helps white and red blood cells to proliferate. [Read more High and low levels of magnesium raises dementia risk]

Therefore, Prof. Tsai and team sought to find a way to target only the HDAC2 activity that impedes memory. They achieved this by looking for proteins that help HDAC to bind to the relevant genes.

The researchers found more than 2,000 genes more likely involved with the activity of HDAC2, by examining gene expression data taken from post-mortems of individuals who were not suffering from Alzheimer’s disease. Some of these individuals had high levels and some had low levels of HDAC2.

The post-mortem samples taken from brains of Alzheimer’s patients showed a strong connection between HDAC2 levels and sp3.

Prof. Tsai believes further work is needed, for example, finding a smaller version of the molecule, before the scientists can set their eyes on an acceptable experimental drug candidate.

The study is published in the journal Cell Reports.

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Salahuddin Ahmed is a freelance medical writer and blogger, who has been writing about medicine and health for more than a decade. A former New York transplant, he now lives in his native Dhaka. He received a Bachelor's degree from the University of Louisiana and a diploma on eTechnology from NIIT, Dhaka. A voracious eater, Salahuddin only dines at restaurants that offer free refills on rice.