Liver-produced amyloid proteins can cause neurodegeneration in the brain, according to a new study in open access journals PLOS BiologyBy John Mamo and his colleagues at Curtin University in Bentley, Australia. The results suggest that the liver may play an important role in the development or progression of the disease, as this protein is thought to be an important factor in the development of Alzheimer’s disease (AD).
Deposition of amyloid beta (A beta) in the brain is one of the pathological features of AD and is involved in both neurodegeneration. Human patient And animal models disease.. However, A-beta is also present in peripheral organs, and blood levels of A-beta correlate with cerebral amyloid loading, Cognitive decline, Increases the likelihood that peripherally produced α-beta contributes to the disease. It was difficult to test that hypothesis because the brain also produces A-beta and it is difficult to distinguish proteins from the two sources.
In the current study, the authors overcame that challenge by developing mice that produce human α-beta only in liver cells. They showed that proteins are carried into the blood by triglyceride-rich lipoproteins, similar to humans, and are passed from the periphery to the brain. They found that mice develop neurodegeneration and cerebral atrophy, which are associated with neurovascular inflammation and cerebral capillary dysfunction. Both of these are commonly observed in Alzheimer’s disease. Affected mice performed poorly in learning tests that depended on hippocampal function. Brain structure It is essential for the formation of new memories.
The results of this study show that peripherally-derived A-beta has the ability to cause neurodegeneration, suggesting that liver-produced A-beta is a potential cause of human disease. doing. If that contribution is important, the findings may have key implications for understanding Alzheimer’s disease. To date, most models of this disease have focused on overproduction of the brain in A-beta, which mimics the rare genetic cases of human Alzheimer’s disease. However, in the majority of AD cases, overproduction of A-beta in the brain is not considered to be central to the pathogenesis of the disease. Instead, lifestyle factors can play a more important role. High-fat diet, May accelerate liver production of A-beta.
Effects of peripheral A beta brain Capillaries may be important in the process of illness, Mamo adds. “Currently, further research is needed, but the finding is that the abundance of these toxic protein deposits in the blood may specifically target the human diet and lipoprotein amyloid. It shows that the drug may be able to deal with it. ”
Lam V, Takechi R, Hackett MJ, Francis R, Bynevelt M, Celliers LM and more. (2021) Liver-only synthesis of human amyloid results in neurodegenerative phenotypes such as Alzheimer’s disease. PLoS Biol 19 (9): e3001358. doi.org/10.1371/journal.pbio.3001358
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