Dr. Haytem Amal from the Faculty of Medicine developed an innovative method that will lead to the development of targeted treatments for various neurological disorders
Nitric oxide (NO) is an important signaling molecule that regulates the actions of various organs, including the brain. S-nitrosylation (SNO), a process of modification of a protein by nitrogen oxide, which includes its attachment to the end of an amino acid called cysteine, is a main mechanism in the transmission of signals in a nerve cell. Dr. Haitam Amal, head of the laboratory for neuro-omics, signal transduction, and translational medicine at the Faculty of Medicine at the Hebrew University, developed an innovative method in the field of mass spectrometry several years ago during his postdoctoral period at MIT, which characterizes substances according to their mass and identifies proteins that have undergone the process of SNO. Combined with computational biology, the method recently yielded two breakthroughs in brain research published in the journals Biomedicines and Scientific Reports.
The first study, published in Biomedicines, revealed for the first time significant gender differences in the biological functions affected by NO and SNO in the cortices of mice. Most of the experimental studies are done on male animals, although there are significant differences between males and females in the mechanisms involved in signal transmission. In order to reveal the differences, Dr. Amal and his team used a method he developed in conjunction with computational biology - and indeed the study showed that there is a significant change created by SNO in various neural and synaptic processes in female mice, and on the other hand processes in the cytoskeleton affected by SNO in male mice. Dr. Amal: "We studied molecular and biological processes in both sexes and found a significant difference and different processes that are affected by SNO between males and females. This study provides us with insights into the roles of the S-nitrosylation process in males and females, which provides strong evidence for gender differences in many biological processes and signaling pathways, which will open future research directions on male-female differences in neurological disorders."
The mass spectrometry method developed by Dr. Amal helped him reach another breakthrough in detecting the changes associated with brain aging. Cell aging depends on the rate of accumulation of oxidative and nitrogenous damage to DNA and proteins. Cumulative data indicate the involvement of a protein that has undergone the SNO process in various brain disorders, however, the changes and involvement of SNO in the brain's development process from young to adult and its aging process are still unknown. In a study published in the journal Scientific Reports, Dr. Amal used his method to examine the set of proteins that underwent the SNO process in young and adult mice, both in the cerebral cortex and in the striatum (an area of the brain attributed to the role of planning and controlling movement and involvement in other cognitive processes). . "Significant biological processes and protein aggregates associated with expression in nerve cells were enriched in adult mice," explained Dr. Amal and continued "extensive quantitative analysis revealed a large variety of proteins that have the potential to be disease factors, which were significantly increased in adult mice. "Our approach, together with large-scale computational biology allowed us to perform system-level characterization and identification of key proteins and biological processes that could be drug targets for aging and brain disorders in future studies"
"The mass spectrometry method we developed together with tools of computational biology, biochemistry, pharmacology, and behavior has already yielded several breakthroughs in the field of autism and Alzheimer's and the hand is still tilted" added Dr. Amal. "We hope that the information that we have succeeded and will be able to provide through the various research tools at our disposal, will lead in the future to a more efficient and accurate development of drugs for neurological diseases."
More of the topic in Hayadan:
- A Technion student developed an innovative method for functional mapping of the cerebral cortex during brain surgery
- It is possible that the period of time in which the auditory cortex is organized is longer than previously thought
- "The energy budget of the brain is constant - this is the reason why 'perceptual blindness' is caused, which causes accidents"
