Oct. 29, 2020

A Ben-Gurion University of the Negev researcher has suggested a common cause of neurodegenerative diseases, which could serve as a guide for developing treatments. Prof. Stas Engel (pictured below) and his team believe the central nervous system of primates has a weak point – a quality control system that clears out poisonous proteins created during high oxygen intake activities. When the system experiences an anomaly, such as trauma or old age, it fails to clean out all of the poisonous proteins, which build up in the neurons and become neurodegenerative diseases.
Stas Engel.JPG
Photo Credit: Nachiyappan Venkatachalam

He and his team published their findings in the September issue of Redox Biology.

Prof. Engel is a member of the Department of Clinical Biochemistry and Pharmacology​ in the Faculty of Health Sciences at BGU.

The key to neurodegenerative diseases may lie in the complexity of the central nervous system of primates. In order to complete so many mental tasks, the brain consumes a lot of oxygen, which results in the production of a high level of reactive oxygen species (ROS), which are poisonous substances. That process is accompanied by the production of damaged proteins, which, if not purged from the body, will begin to accumulate and damage neurons and supporting cells. Primates, as indicated in the study, have developed an extra level of defense mechanisms to combat ROS, namely ‘primate differential redoxome’ (PDR), which is absent in lower organisms. The PDR makes the nervous system of primates extremely robust in the face of ROS. However, the downside of robustness is fragility. Nonroutine events may cause the PDR to fail, thereby letting the ROS into the brain.

"One of the anomalies the PDR system must deal with is old age. We are living much longer than we used to and therefore, the system cannot keep up. Physical trauma could also represent an anomaly that disrupts the PDR's routine processing," says Prof. Engel.

"These findings indicate that the predisposition of the human brain to neurodegeneration is engraved in our genes, therefore treatments for neurodegenerative diseases will be difficult. Our discovery could help lay the groundwork for future treatments by showing which system to target," he adds.

Additional authors include Prof. Engel's students Nachiyappan Venkatachalam, Shamchal Bakavayev, and Daniel Engel and Prof. Zeev Barak of the Department of Life Sciences in the Faculty of Natural Sciences.

This research was supported by the Israel Science Foundation (Grant No. 343/16).

Photo Credit: Nachiyappan Venkatachalam