Your brain like a great orchestra emphasis on the perfect coordination of many elements to function properly. If one elements don’t ordinate another elements it effects entire of body. For instance in Alzheimer’s disease damage to specific neurons can change brainwave rhythms and cause a loss of cognitive functions.

One type of neuron that we called inhibitory interneuron is very important for managing brain rhythms. It’s the research focus of a laboratory led by Jorge Palop, PhD, assistant investigator at the Gladstone Institutes. In a study published in Neuron, Palop and his collaborators uncovered the therapeutic benefits of genetically improving these interneurons and transplanting them into the brain of a mouse model of Alzheimer’s disease. Interneurons control a set of networks between neuron allowing them to send signals to one another neuron until in a harmonized way. You can consider inhibitory interneurons as orchestra conductors. They create rhythms in the brain to instruct excitatory neurons when to play and when to stop.

An unbalance between these two types of neurons creates disaccord and is seen in multiple psychiatric and neurological disorders, including Alzheimer’s disease, schizophrenia, autism and epilepsy.

A Brain without a Conductor

Palop’s previous studies illustrated that in mouse models of Alzheimer’s the inhibitory interneurons do not work properly. So the rhythms that arrange the excitatory cells are fail and disturbed to function harmoniously, causing an unbalance in brain networks. This, in turn, affects memory organization and can lead to epileptic activity which is often saw in patients with Alzheimer’s disease.

His team found a path to reengineer repressive interneurons to improve their function. They illustrated that these increased interneurons when transplanted into the abnormal brain of Alzheimer mice can control the activity of restitute brain rhythms and excitatory cells.

Palop, who is also an assistant professor of neurology at the University of California, San Francisco, said:

We took advantage of the fact that transplanted interneurons can integrate remarkably well into new brain tissues, and that each interneuron can control thousands of excitatory neurons. These properties make interneurons a promising therapeutic target for cognitive disorders associated with brain rhythm abnormalities and epileptic activity.

First the scientists had to overcome a remarkable challenge. When they transplanted regular interneurons, they saw no beneficial effects, likely because Alzheimer’s disease creates a toxic environment in the brain. The researchers then genetically enhanced the activity of inhibitory interneurons by adding a protein called Nav1.1. They discovered that the interneurons with boosted function were able to dominate restore brain function and the toxic disease environment. Palop said:

These optimized neurons are like master conductors. Even with a declining orchestra, they can restore the rhythms and harmony needed for cognitive functions. 

Conductors Engineered for Alzheimer’s Disease

The findings could finally lead to the development of new cure options for patients with Alzheimer’s disease. Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease said:

Besides the applications this cell engineering and transplantation approach may find in regenerative medicine, our findings support the broader concept that enhancing the function of interneurons can counteract key aspects of Alzheimer’s disease.

Moreover to investigating whether the cell therapy could be translated from mice to humans. Palop and his colleagues are working to recognize potential medicines as an alternative way to increase the functions of inhibitory interneurons. Elizabeth Edgerly, PhD, executive director of the Alzheimer’s Association, Northern California and Northern Nevada chapter said:

Advancing our understanding of Alzheimer’s disease and identifying potential new treatment strategies are critical to addressing the escalating global health crisis. We were proud to support Dr. Palop’s research and vision with an Investigator Initiated Research Grant award.

The Alzheimer’s community that provided part of the study and this association is the world’s largest private provider of Alzheimer’s research.


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