WHAT IS IT…AND WHY DOES IT MATTER?
What is it? Autophagy is our cells' garbage disposal - the process by which our cells disassemble and recycle unneeded and defective components. The word autophagy derives from the Greek auto (self) and phagein (to eat), and this etymology paints a fairly accurate picture of how autophagy works: a cell eats part of itself, discards the waste, and recycles the nutrients.
In practice, autophagy requires multi-step precision to function correctly. The defective or unusable component must be properly identified by and isolated within an organelle called an autophagosome, which carries the target component through the cell and eventually fuses it with the lysosome, the organelle responsible for waste disposal. Along every step of the way, the process is directed by autophagy-related proteins in the cell.
Efficient autophagy is crucial to the function of a healthy cell. Without this process, a cell would become overwhelmed by malfunctioning parts and waste materials.
Why does it matter? Recent large-scale genomic studies have identified several new genes that are mutated in ALS, and a large portion of these—including TBK1, UBQLN2, p62, optineurin, and VCP—are involved in directing the autophagy process.
While researchers have long known that a hallmark of ALS and related brain diseases is the accumulation of protein clumps that disrupt normal cell function—activating inflammatory and immune responses and ultimately leading to cell death—efforts to clear these proteins using drugs have not been successful in actually slowing these diseases in patients. Targeting autophagy may hold the key. If we can fix the disruptions in autophagy in ALS, cells will be better able to clear these harmful protein aggregates on their own, restoring normal function and slowing or stopping the ALS disease process.