Beersheba Researcher Proposes Common Cause of Neurodegenerative Diseases

Neurons (nerve cells) are the building blocks of the central nervous system, which includes the brain and spinal cord. Neurons normally don’t reproduce or replace themselves, so when they become damaged or die, they cannot be replaced by the body.

When neurons fail, neurodegenerative diseases including Parkinson’s, Alzheimer’s, which are the most common among them and affect 10% and 2%, respectively, of the population over 65 in the US alone, occur.  These are incurable and debilitating conditions that result in progressive degeneration and/or death of nerve cells. This causes problems with movement (called ataxias) or mental functioning (called dementias), which are responsible for the greatest burden of neurodegenerative diseases. Alzheimer’s disease comprises between 60% and 70% of dementia cases.

Other neurodegenerative disorders include multiple sclerosis, prion disease, motor motor neurone diseases, Huntington’s disease, spinocerebellar ataxia and spinal muscular atrophy. Although the symptoms of various neurodegenerative diseases are quite different, some of the more common symptoms of neurodegenerative diseases include memory loss., apathy, forgetfulness, anxiety, mood changes, agitation and a loss of inhibition.

Now, a researcher at Ben-Gurion University (BGU) of the Negev in Beersheba has suggested a common cause of neurodegenerative diseases – which could serve as a guide for developing treatments.

Prof. Stas Engel and his team in the department of clinical biochemistry and pharmacology in the Faculty of Health Sciences believe that the central nervous system in primates, including humans has a weak point – a quality control system that clears out poisonous proteins created during high oxygen intake activities. When the system experiences a deviation such as trauma or old age, it fails to clean out all of the poisonous proteins that build up in the neurons and become neurodegenerative diseases.

He and his team published their findings recently in the journal Redox Biology under the title: “Primate differential redoxome – A paradigm for understanding neurodegenerative diseases.”

The key to neurodegenerative diseases, they wrote, may lie in the complexity of the central nervous system of primates. 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 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 vigorous in the face of ROS. But 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 cope 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,” explained Engel.

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

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