Autophagy is a word derived from the Greek that literally means “eating the self.” In terms of your body, autophagy is a process whereby cells will destroy misfolded proteins or breakdown faulty components and then recycle what’s left — essentially, it’s the garbage disposal system of your cells and is a necessary part of your body’s survival.

But in some cases the process becomes disordered and causes disease. In particular, autophagy is believed to be disrupted in patients with Alzheimer’s disease (AD) and is thought to cause the signature build-up of protein plaques that clog the brain. Now, a new study from researchers at Kyungpook National University suggests unclogging the body's protein disposal system could help patients with AD and even improve their memory.

Discovery May Help Researchers Develop New Drugs

Alzheimer’s disease involves not just one faulty biochemical function within brain cells but many. These cause progressive brain damage and lead to dementia and memory loss. Though no one knows exactly how AD begins, scientists understand it to be a complex interaction between genes and the environment. In previous studies, a team of researchers from Kyungpook National University discovered how the brains of Alzheimer’s patients have elevated levels of an enzyme called acid sphingomyelinase, or ASM for short. This enzyme, which is expressed by almost all cell types, normally works in harmony with other enzymes and proteins for proper cell metabolism; yet at the wrong levels, it breaks down membrane lipids in the myelin sheath that coats nerve endings.

Although the research team had been aware of a link between ASM and Alzheimer’s, they wanted to know if it might be directly causing AD. So they examined ASM and the activities and levels of various lipids in brain tissue samples from Alzheimer’s patients and a group of unaffected individuals. As expected, they confirmed a significantly higher level of ASM in patients with AD compared with normal individuals. Then, they took their experiment one step further and looked at ASM levels in samples from individuals with Parkinson’s disease. What did they observe? ASM was not elevated in samples from Parkinson’s patients — elevated levels of ASM, they decided, must be a signature of Alzheimer’s disease alone.

Next, the team of researchers ran experiments to figure out how ASM and AD co-exist. This time the team turned to mice with Alzheimer’s-like disease and elevated levels of ASM activity. After testing and analysis, the researchers found the additional ASM appeared to clog up the autophagy machinery in the brain cells of the mice. In turn, this resulted in an accumulation of waste. When they reduced the levels of ASM in the mice by using the drug amitriptyline-hydrochloride, the researchers were able to restore proper autophagy and this lessened the brain damage in the mice. Eventually, the mice even showed improved learning and memory.

The researchers hope the same holds true for humans. That would mean a drug could be developed to interfere with ASM activity and so effectively slow — and maybe even reverse — neurodegeneration in patients with AD.

 

Source:  Lee JK, Jin HK, Park MH, et al. Acid sphingomyelinase modulates the autophagic process by controlling lysosomal biogenesis in Alzheimer’s disease. JEM. 2014.