Scientists from the University of California, San Francisco laboratory used a compound found in the anti-wrinkle cream to prevent the death of nerve cells caused by the genetic mutation of hereditary Parkinson's disease. A similar approach may be able to prevent cell death in the brain of patients with Parkinson's disease. The research team published the study online in the August 15 issue of Cell.
Kevan Shokat, Ph.D., a senior researcher at the study and a chemist at the University of California, San Francisco, said that this is the first time that the activity of a kinase is highly specifically targeted to increase rather than inhibit the activity. The new research brings hope to the possibility of using similar pharmaceutical strategies to fight against other diseases such as diabetes and cancer.
The mutation leads to dysfunction of the target enzyme PINK1, which is a direct cause of some cases of early-onset Parkinson's disease. Loss of PINK1 activity damages the cell's power plant: mitochondria. As we all know, mitochondria can convert food energy into another form of chemical energy used by cells-molecular ATP. In Parkinson's disease, mitochondrial dysfunction is related to the death of dopamine-producing neurons in the substantia nigra of the brain, and the substantia nigra plays an important role in controlling movement. Dopaminergic neuronal cell death is a hallmark of Parkinson's disease, the cause of significant symptoms such as rigidity and tremor.
Under Shokat's leadership, researchers at the University of California, San Francisco used a compound called kinetin to increase the activity of the mutant PINK1 enzyme in nerve cells to near normal levels. "Since the mutation of PINK1 in humans has caused Parkinson's disease, it was found that kinetin can increase the activity of the mutant kinetin to near normal levels, and proposed the possibility of using kinetin to treat these patients," Shokat said.
The researchers also found that in nerve cells with normal PINK1, kinetin increased enzyme activity to exceed standard levels. This study found that it may be related to the most common form of Parkinson's disease. PINK1 is not mutated in this type of disease. Previous studies have confirmed that similar PINK1 overactivation can slow another kind in the Drosophila Parkinson's disease model Abnormal movements caused by defects. This defect increases alpha-synuclein protein production, which is also the cause of some cases of hereditary Parkinson's disease. Shokat said the new study confirmed that PINK1 can be increased in human nerve cells lacking PINK1 mutations, thus indicating that kinetin may also have therapeutic potential in common Parkinson's disease without PINK1.
Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's disease. According to statistics from the US Centers for Disease Control and Prevention, it is the 14th leading cause of death in the United States. Current treatments are focused on improving the utilization of dopamine in brain regions where dopamine-producing nerve cells are lost. Shokat said that although many drugs have been developed to inhibit kinase activity in the past 10 years, there are currently 15 drugs approved for the treatment of cancer, and there are currently no drugs that directly promote kinase activity on the market.
Shokat used a non-traditional method to make breakthroughs, using drugs to increase the activity of PINK1. He targeted the "substrate" of the enzyme, and the substrate molecule bound to the enzyme would undergo a rapid chemical transformation. The substrate used by PINK1 is ATP, a chemical reaction that helps PINK1 in turn drive the activation of another enzyme, Parkin. Both enzymes have previously been shown to be closely related to Parkinson's disease. PINK1 and Parkin work together to monitor the health of mitochondria, help to initiate repairs or remove damaged mitochondria in cells, and thus promote cell survival.
"Since scientists did not expect to develop a new substrate for this enzyme in the past, they did not consider the use of therapeutic methods to increase the activity of PINK1," Shokat said. "We found that compared to the natural substrate ATP, a small molecule called KTP can accelerate the chemical reaction catalyzed by PINK1. This superior natural reaction is unheard of."
Shokat said that KTP is too large for other kinases, but PINK1 has a larger ATP "pocket" to accommodate KTP. After discovering the potential of KTP, the study determined that kinetin can be converted to KTP in the cell. Experiments show that kinetin can enter the brain through blood vessels. At present, kinetin has been used for oral administration to treat a rare genetic neurological disease called familial autonomic dysfunction.
Made of supreme quality EVA material, water resistant, moisture proofing and dust-proof.
Comfortable fuzzy lining, soft shock absorbing protection against minor bumps drops and shocks, reduce damages caused by accidentally bumping.
Durable metal zipper, smooth but strong 360.degree zipper, provides durability and a long-lasting performance.
Vr Case,Eva Vr Case,Vr Glasses Eva Case,Eva Tool Case For Vr
Shenzhen Guohui Craft Products Co.,Ltd. , https://www.evacarrycase.com