Are the very systems that are supposed to dispose of cellular waste making it worse? Are you looking to learn about how to fix a garbage disposal? A study at Yale University in New Haven, Connecticut, thinks that might be the case in terms of lysosomes and the amyloid plaques that are believed to cause Alzheimer's disease. The study, published in the Proceedings of the National Academy of Sciences and reported in Medical News Today, refutes the idea that massive accumulations of lysosomes surrounding beta-amyloid deposits in the brains of people with Alzheimer's disease are helping to degrade and remove the faulty protein. Instead, say the Yale researchers, the lysosomes are making it worse (http://www.medicalnewstoday.com/articles/296207.php).
According to the National Center for Biotechnology Information of the national Institutes of Health, lysosomes are "membrane-enclosed organelles that contain an array of enzymes capable of breaking down all types of biological polymers - proteins, nucleic acids, carbohydrates, and lipids." Functioning as the cell's digestive system, lysosomes degrade material taken up from outside the cell and digest obsolete components of the cell (http://www.ncbi.nlm.nih.gov/books/NBK9953/).
Alzheimer's disease, the most common form of dementia,affects the part of the brain that controls thought, memory and language. Affecting as many as 5 million Americans aged 65 years or older in 2013, it could rise to 13.8 million by 2050, according to the Centers for Disease Control. The Yale team's discovery could lead to new types of treatment that correct the faulty lysosomes, enabling them to do their job properly, clear away the beta-amyloid and keep it from clogging the brain.
The researchers explain that the lysosomes accumulate in swollen axons or nerve fibers that contact the amyloid deposits outside of the brain cells. The lysosomes have unusually high levels of beta-secretase, the enzyme that triggers the production of the toxic beta-amyloid protein. They are unable to break down the enzyme, because they are not fully mature. To achieve maturity, they have to move along the axons. When the beta-amyloid plaques block the lysosomes from traveling along the axons, there is a larger accumulation of beta-secretase, which in turn brings about additional beta-amyloid production. According to first author Swetha Gowrishankar, a postdoctoral scientist in the lab of senior author Shawn Ferguson, assistant professor of cell biology, "We think this represents a vicious circle."
To eliminate the enzyme that increases Alzheimer's plaques, the lysosomes have to be able to travel and mature. However, their ability to do so is hampered by Alzheimer's plaques. Faulty lysosomes have also been implicated in other neurodegenerative diseases including Parkinson's and frontotemporal dementia, the researchers say.The Howard Hughes Medical Institute, the Ellison Medical Foundation, the National Institutes of Health and the Consortium for Frontotemporal Dementia Research funded the study.
Neuroscience
JUL 03, 2015