动物实验,帕金森氏症,痴呆症 z-bo 2020-11-23 308

　　Prescription drugs for the treatment of hypertension have shown promise for diseases such as Parkinson's disease, Huntington's disease and dementia in studies conducted on mice and zebrafish at the University of Cambridge.

　　A common feature of these diseases-collectively called neurodegenerative diseases-is the accumulation of misfolded proteins. These proteins, such as Huntington's protein in Huntington's disease and tau in some dementias, form "aggregates" that can cause irreversible damage to nerve cells in the brain.

　　In healthy individuals, the body uses a mechanism to prevent the accumulation of this toxic substance. This mechanism is called autophagy or "self-eating", and involves'Pac-Man'-like cells eating and breaking down materials. However, in neurodegenerative diseases, this mechanism is impaired and unable to clear the accumulated protein in the brain.

　　With the aging of the global population, more and more people are diagnosed with neurodegenerative diseases, making it more urgent to find effective drugs. However, there is currently no drug that can effectively induce autophagy in patients.

　　In addition to finding new drugs, scientists often seek to reuse existing drugs. Their advantage is that they have been proven safe for human use. If they can be proven to be effective for the target disease, then the process of clinical use is much faster.

　　In a study published today in the journal Nature Communications, scientists from the Institute of Dementia in the United Kingdom and the Cambridge Institute of Medicine at the University of Cambridge found in mice that the hypertension drug felodipine may be a drug candidate for reuse.

　　Epidemiological studies have suggested that there may be a link between the drug and the reduced risk of Parkinson's disease, but now researchers have shown that it may induce autophagy in several neurodegenerative diseases.

　　The research team led by Professor David Rubinsztein used genetically modified mice to express mutations that cause Huntington’s disease or a certain Parkinson’s disease, and zebrafish mimic a type of dementia.

　　mice are useful models for studying human diseases, because they have a short life span and a fast reproductive rate, so they can study biological processes in many areas. Their biology and physiology have many of the same important characteristics as humans, including a similar nervous system.

　　Felodipine can effectively reduce the accumulation of mouse aggregates in mutant mice with Huntington's disease, Parkinson's disease, and zebrafish dementia models. The treated animals also showed fewer signs of disease.

　　Research on mice usually uses doses much higher than those known to be used safely in humans. Professor Rubinsztein and colleagues showed in Parkinson's disease mice that even at concentrations similar to those tolerated by humans, they may show beneficial effects. They did this by using small pumps under the skin of mice to control the concentration.

　　"This is the first time we are aware of a study showing that an approved drug can slow the accumulation of harmful proteins in the brains of mice, using a dose that mimics the concentration of the drug seen in the human body," said Professor Rubinstein . "Therefore, the drug can slow the progression of these potentially destructive diseases, so we think it should be tested on patients."

　　"But this is only the first stage. This drug needs to be tested on patients to see if it produces the same effects in humans as in mice. We need to be cautious, but I want to say that we can be cautious and optimistic."