Researchers at Tel Aviv University deciphered the mode of action of IGF-1R, a receptor associated with life expectancy, Alzheimer's, cancer and other phenomena
Groundbreaking research from Tel Aviv University opens a window into understanding the function and role of an essential receptor, found in every cell in our body. The new insights may be used as a basis for developing future treatments for Alzheimer's, and even for slowing down the aging process.
The receptor, whose scientific name is IGF-1R, has long been known to researchers as a multifunctional protein, involved in many processes: starting with the development of fetuses and the growth of children, through cancerous tumors, and ending with aging. A group of researchers from Tel Aviv University, led by Dr. Ina Slutsky from the Faculty of Medicine and Sagol School of Neuroscience, set out to investigate the way IGF-1R works in the brain, and the relationship between it and Alzheimer's disease, which characterizes old age. The basic research, which dealt with the level of the molecules and the individual cell, revealed a deep and essential layer in the activity of the brain - both in a normal state, and in diseased states.
The research was actually carried out by doctoral student Neta Gazit, in collaboration with researchers Dr. Irena Vertkin, Dr. Ilana Shapira, Aden Shlomowitz, Maayan Shaiva and Yael Mor from Dr. Slutsky's laboratory, and with researchers from the University of Göttingen in Germany.
The study was published in the journal Neuron in February 2016.
Transfer of information between nerve cells
"In 2009, two studies were published that showed that a decrease in the amount of the IGF-1R receptor is associated with an improvement in brain function and a weakening of Alzheimer's-related pathology in mice in an Alzheimer's model," says Dr. Slutsky. "We wanted to find out why and how this happens, but at the very beginning of our work we found that very little is known about the activity of IGF-1R in the transmission of information in the brain in general - and first of all in the healthy brain. That's why we decided to 'take a step back', and examine the action and effect of the receptor in the brain - first in a normal state, and only later in the state of Alzheimer's."
The researchers focused on the hippocampus, the same area of the brain responsible for memory and learning, which is known to be significantly damaged in Alzheimer's patients. Using brain slices and cultures of hippocampus cells, they examined in the laboratory the reaction of the receptor to various proteins, and the effect of the procedures on the passage of information in the synapses - the connection points between the nerve cells in the brain.
Dr. Slutsky explains: "We know two types of information transfer between the nerve cells in the brain: the great majority of the activity is the transfer of clear and identifiable information, resulting from electrical stimulation; In addition, there is also a small amount of spontaneous and random information transfer, without electrical stimulation, whose function we do not know, and is sometimes referred to as 'noise'. The most interesting finding in our study was the effect of an inhibitory substance, which reduces the activity of IGF-1R, on both types of information transmission: we discovered that when the receptor is inhibited, there is a decrease in information transmission resulting from electrical stimuli, and in contrast, an increase in spontaneous information transmission. The general result is a significant decrease in the overall activity of the brain." Later, the researchers revealed two molecular mechanisms that mediate these phenomena, which are found in the cell's mitochondria (an organelle that produces energy, and is considered the 'powerhouse' of all body cells).
A new approach to Alzheimer's
Dr. Slutsky summarizes: "One of the known phenomena in people at risk of Alzheimer's is increased and abnormal activity of the nerve cells in the hippocampus. We have shown that the addition of an IGF-1R inhibitor, which causes a decrease in the activity of the receptor, also reduces the activity in the synapses of the neurons in the hippocampus. Therefore, we now recommend testing the effectiveness of the inhibitory substance as a new approach to treating abnormal brain activity, which causes cognitive failure in Alzheimer's patients. In addition, since it is known that the risk of Alzheimer's disease increases with age, and IGF-1R plays a central role in determining life expectancy, there may be a first step in understanding the causal relationship between brain activity and aging, and hence the development of additional drugs that will prolong our lives."
One response
This is Dr. Ina Slutsky, the researcher, not Ilana Slutsky