From Myelin Loss to Memory Decline: How Chronic Cellular Stress Drives Neurodegeneration

Pelizaeus-Merzbacher disease (PMD), is a rare neurological disorder that disrupts myelin in the brain. A mutation in the PLP1 gene affects oligodendrocytes which are the cells that produce myelin. When PLP becomes mutated, it results in a build up inside the cell and stress becomes a factor in the endoplasmic reticulum. To counteract the stress, the body has an integrated stress response (ISR) to protect itself from any harm. In PMD, the ISR is activated for longer than it needs to be and ends up doing more harm than good which ends up killing the cells its supposed to protect. As oligodendrocytes die, myelin production stops and the brain enters a state of hypomyelination. In a study by Yanan Chan et al., researchers used a mouse model to discover, that deleting a protein named PERK reduced ISR activity. This resulted in the mice living two weeks longer with improved myelination. Over working the ISR can do the opposite of what its supposed to and actually drive the progression of dis...