SCF蛋白复合物,α-突触核蛋白聚集物 z-bo 2020-10-26 360

　　In a new study, researchers at the Swiss Federal Institute of Technology in Zurich, Zurich University Hospital, and the University of California San Diego have discovered a new mechanism by which brain cells can protect themselves from protein aggregation. Brain nerve cell α-synuclein (α-synuclein) aggregates play an important role in Parkinson's disease and other neurodegenerative diseases. The quality of these proteins will spread between nerve cells and make the disease worse.

　　Now, these researchers have discovered how the body removes these destructive protein aggregates. Their findings may open up new ways to treat neurodegenerative diseases. These diseases are related to long and thin fibers or fibrils, and a large number of α-synuclein molecules accumulate in these fibrils. However, a single non-aggregating α-synuclein molecule is the key to healthy brain function because the protein plays an important role in the release of the neurotransmitter dopamine in the synapses of nerve cells. When this protein changes its three-dimensional shape and aggregates into the fibrils of nerve cells, it no longer performs its normal function. These fibrils are also toxic to nerve cells. After that, the cells that produce dopamine die, and the brain cannot provide enough dopamine, causing the typical clinical symptoms of Parkinson's disease, such as muscle tremor.

　　Decoding the degradation mechanism Paola Piccotti is

　　The co-author of the paper, Professor of Protein Network Biology at ETH Zurich, explained that the molecule, the latter, then combines together to change its own shape. This is a method in which these fibrils infect cells in turn and are thought to occupy all areas of the brain over time. A study she imagined. The research was led by her former postdoctoral researcher Juan Geres. These researchers can also decipher the cellular mechanism that spontaneously degrades α-sinucrane fibrils. A protein complex called SCF can specifically detect α-sinucrane fibers and direct them to known cell destruction mechanisms. In this way, the spread of these fibrils is blocked, as demonstrated in mouse experiments. When SCF is turned off, there are no longer alpha-synuclein fibrils in nerve cells. It may be deleted. Instead, they accumulate in these cells and spread throughout the brain. Stem cell or gene therapy Picotti and Geres believe that this SCF degradation mechanism is expected to be used in therapy. Geres said: "The higher the degree of activation of the SCF complex, the more αsinucrane fibrils are removed, which can slow down or ultimately prevent the development of this neurodegenerative disease."

　　The object's existence is very short, and will disappear within a few minutes. The focus of treatment is to maintain the stability of this complex and enhance its ability to interact with α-synuclein fibrils. For example, drugs can be developed for this purpose. Picotti says that another way to help Parkinson's disease patients is to transplant neural stem cells into the brain. She explained that previous attempts were not successful because alpha-synuclein fibrils in the brain infected these healthy stem cells. She said: "If these stem cells can be modified so that they are not disturbed, or the fibers that enter them can be quickly broken down, then this will promote the development of stem cell therapy. It is possible." It can be used to stabilize the SCF complex of nerve cells. To increase its activity. Geres said: "But the potential treatment is still in its infancy, and it is not clear whether an effective treatment can be developed."