A Different Take on a Cellular Garbage Catastrophe in Neurodegeneration

The garbage catastrophe view of aging in long-lived cell populations with little turnover, such as those of the brain, is fairly well established. Over-simplifying somewhat, it is a downward spiral in which accumulated molecular damage and metabolic waste in cells makes their maintenance processes ever less efficient, which in turn leads to a faster increase in damage and waste. That ultimately leads to cellular senescence, or programmed cell death, or other forms of dysfunction. Here, researchers present a somewhat different take on a garbage catastrophe, one in which cells sabotage one another by ejecting waste and damaged proteins into the surrounding environment:

Neurodegenerative diseases like Alzheimer's and Parkinson's may be linked to defective brain cells disposing toxic proteins that make neighboring cells sick. Researchers found that while healthy neurons should be able to sort out and rid brain cells of toxic proteins and damaged cell structures without causing problems, this does not always occur. These findings could have major implications for neurological disease in humans and could possibly be the way that disease can spread in the brain. "Normally the process of throwing out this trash would be a good thing. We think that there might be a mismanagement of this very important process that is supposed to protect neurons but, instead, is doing harm to neighbor cells."

Scientists have understood how the process of eliminating toxic cellular substances works internally within the cell, comparing it to a garbage disposal getting rid of waste, but they did not know how cells released the garbage externally. "What we found out could be compared to a person collecting trash and putting it outside for garbage day. They actively select and sort the trash from the good stuff, but if it's not picked up, the garbage can cause real problems."

Working with the transparent roundworm C. elegans, which are similar in molecular form, function, and genetics to those of humans, researchers discovered that the worms - which have a lifespan of about three weeks - had an external garbage removal mechanism and were disposing these toxic proteins outside the cell as well. The team realized what was occurring when they observed a small cloud-like, bright blob forming outside of the cell in some of the worms. Over two years, they counted and monitored their production and degradation in single still images until finally they caught one in mid-formation. Roundworms engineered to produce human disease proteins associated with Huntington's disease and Alzheimer's threw out more trash consisting of these neurodegenerative toxic materials. While neighboring cells degraded some of the material, more distant cells scavenged other portions of the diseased proteins.

Link: http://news.rutgers.edu/research-news/alzheimer%E2%80%99s-may-be-linked-defective-brain-cells-spreading-disease/20170212

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