Parkinson’s disease (PD) and Alzheimer’s disease (AD) are the two most common neurodegenerative diseases: an estimated 5 million Americans are living with AD, and PD affects an estimated 60,000 Americans each year. While the two diseases have many differences including risk factors, genetic components, and the structural changes they create in the brain, researchers have recently identified one enzyme that is common to both.1,2
Enzyme linking Parkinson’s & Alzheimer’s: AEP
The enzyme is called asparagine endopeptidase or AEP. In healthy brains, AEP is found only in lysosomes, the structures in the cells that act as a waste removal system, digesting excess or worn out materials, viruses, or bacteria. In people with AD or PD, AEP is found in greater quantity and overflows into other parts of the cell.
Both AD and PD have toxic clumps of protein found in the brain, although the proteins are different. In Alzheimer’s, the protein tau creates tangles. In PD, the protein alpha-synuclein clumps together forming Lewy bodies.
Earlier research done by the team at Emory found that the AEP enzyme cuts tau proteins, which makes the protein more sticky and likely to form the tangles that are characteristic of Alzheimer’s. Researchers followed a hunch that the enzyme would act the same in PD and found they were right: AEP also cuts alpha-synuclein, making it more likely to create the clumps of Lewy bodies.1-3
Why this is important
This research provides an exciting new target for potential therapeutics. By blocking AEP, it’s possible that the degenerative process of clumps or tangles in both neurodegenerative diseases would be slowed or stopped. Researchers are next going to test out various AEP inhibitors in animals with PD. There have already been studies conducted with animal models in Alzheimer’s, with promising results.2,4
Reason for caution
While the animal studies are a necessary step in determining the viability of a potential AEP-blocking therapy, treatments that work in animal models don’t necessarily work in humans. Also, there is some concern that blocking AEP may have unintended consequences for the health of the cell, given AEP’s primary role in cleaning up waste in the cell.
Researchers also note that while AEP is an important enzyme that plays a major role in the development of Lewy bodies in PD, there are likely other enzymes that also cut alpha-synuclein. Additional research will be needed to fully understand the ways in which PD develops and progresses.2,3
Medical News Today. Accessed online on 7/21/17 at http://www.medicalnewstoday.com/articles/318257.php
Zhang Z, et al. Asparagine endopeptidase cleaves α-synuclein and mediates pathologic activities in Parkinson’s disease. Nature Structural and Molecular Biology. 2017; doi: 10.1038/nsmb.3433.
Emory Health Sciences. "Drug discovery: Alzheimer's and Parkinson's spurred by same enzyme: AEP protease acts on amyloid, tau and now alpha-synuclein." ScienceDaily. ScienceDaily, 3 July 2017. Accessed online on 7/21/17 at www.sciencedaily.com/releases/2017/07/170703121032.htm.
IFL Science. Accessed online on 7/21/17 at http://www.iflscience.com/health-and-medicine/one-enzyme-to-rule-us-all-parkinsons-and-alzheimers-have-common-biochemical-origin/