One characteristic of neurodegenerative diseases, such as Huntington, is the progressive death of nerve cells in the brain. However, the cells do not die quickly. They begin to separate first because their neuritis, which is the long, finger-shaped extensions that make connections throughout the brain smaller.
Researchers at the University of Pittsburgh School of Medicine suggest a new mechanism called “neurosis” that could explain the narrowing of neurons in Huntington and other neurodegenerative diseases, opening the door to new therapies. The research was published this week in the journal Proceedings of the National Academy of Sciences.
“Neurosis is a process that has not yet been recognized or described and could play a very important role in normal brain development, neurodegenerative disorders, and aging,” said MD, president and CEO President Robert Friedlander and Professor Walter E. Dandy of Neurosurgery and neurobiology at the Pitt School of Medicine.
It all started when Dr. Sergei Baranov, a scientist in Friedlander’s laboratory, saw an interesting phenomenon in the mouse nerve cells he had grown in the lab.
Researchers have found that when mitochondrial proteins at the tip of neurites are damaged by normal wear and tear, new proteins do not replace them as quickly as mitochondria in the nucleus. This made them less efficient, activating the executor enzymes, caspases, and eventually leading to neuroses.
To test their premonition, the Friedlanders team used genetically altered mice that passed a malformed version of the human huntingtin protein. These mice show indication of the disease, comprising accelerated neuronal death. Their findings were similar to what they had seen in cells but more pronounced. There were fewer mitochondria at the extremities, and what was missing was more dysfunctional than regular neurons. There was also more foundation of caspases and augmented levels of cell death.