Articles selected from the October 2007 issue of Molecular & Cellular Proteomics (Vol. 6, No. 10):
- Preventing neurodegenerative diseases by studying proteins in the brain
- Improving cancer diagnosis
- Improving liver cancer diagnosis
Preventing neurodegenerative diseases by studying proteins in the brain
Researchers report the most complete list so far of the proteins present in the cerebral cortex – the outermost layer of the brain that plays a central role in memory, language, cognition, and consciousness. The cerebral cortex is also the part of the brain that contains the hallmarks of many neurodegenerative diseases, so these results could help understand how such diseases develop and maybe find ways to slow it down.
Most neurodegenerative diseases develop in specific regions of the brain. For instance, loss of neurons due to Alzheimer’s disease (AD) occur mostly in the cerebral cortex and hippocampus, and degeneration of neurons in Parkinson’s disease largely centers on an area in the back of the brain called the brainstem – at least in the early stage of the disease.
Jing Zhang and colleagues identified over 800 different proteins in a part of the cortex near the forehead called the frontal cortex. This region of the brain is involved in many neurodegenerative diseases in which intellectual function deteriorates over time, including AD, Parkinson’s disease with dementia (PDD), and dementia with Lewy body (DLB) disease, and frontotemporal lobar degeneration (FTLD).
The proteins identified in this study perform various functions inside the cell, such as the transport of other proteins, the activation of neighboring proteins, and the catalysis of biochemical reactions. Among these proteins, the scientists found that at least half a dozen are known to be associated with neurodegenerative diseases, but examining the role of the other proteins may show that some of them also are involved in these diseases.
The scientists also found that 17 percent of the identified proteins are also present in the cerebrospinal fluid (CSF) – a watery fluid that surrounds and protects the brain and spinal cord. Since proteins in the CSF are more accessible clinically than those in the cortex, understanding how proteins present in both the frontal cortex and CSF are involved in neurodegenerative diseases could help improve their diagnosis and assess disease progression.
Taken together, the proteins identified in this study provide important information to ultimately understand how the frontal cortex works and what goes wrong in many neurodegenerative diseases, the researchers conclude. Zhang and his team are now trying to determine the most comprehensive list of all the proteins that are working in other brain regions, such as the middle brain, which is heavily involved in movement disorders such as Parkinson’s disease.
Article: “Proteomics Identification of Proteins in Human Cortex Using Multidimensional Separations and MALDI Tandem Mass Spectrometer,” by Sheng Pan, Min Shi, Jinghua Jin, Roger L. Albin, Andy Lieberman, Marla Gearing, Biaoyang Lin, Catherine Pan, Xiaowei Yan, Daniel T. Kashima, and Jing Zhang
MEDIA CONTACT: Jing Zhang, University of Washington School of Medicine, Seattle, Washington; tel: 206-341-5245; e-mail: zhangj@u.washington.edu
Improving cancer diagnosis
Researchers have developed a new way of detecting the abnormal presence of complexes of sugars and proteins in the blood of cancer patients, thus providing a new tool for cancer diagnosis.
Many proteins on the surface of cells have sugars attached to them, which helps the cells bind with one another and communicate among one another. But in cancer, these cell surface proteins can have an abnormally high number of sugar molecules attached to them.
Martin R. Larsen and colleagues report a method that uses titanium dioxide to isolate the parts of the cell surface proteins that are attached to sialic acid, which is the “outside” portion of some of the sugars that are attached to these proteins. The method was used to compare the number of protein-sugar structures that contain sialic acid in the blood plasma of a control individual and a patient with advanced bladder cancer. The scientists showed that the cancer patient’s blood contained a significantly higher number of these sialic acid-containing structures than the control individual.
This method is a promising way to diagnose cancer and other diseases with excess sialic acid-containing protein-sugar structures, the scientists conclude.
Article: “Exploring the Sialiome Using Titanium Dioxide Chromatography and Mass Spectrometry,” by Martin R. Larsen, Soren S. Jensen, Lene A. Jakobsen, and Niels H.H. Heegaard
MEDIA CONTACT: Martin R. Larsen, University of Southern Denmark, Odense, Denmark; tel: +45 6550 2475; e-mail: mrl@bmb.sdu.dk
Improving liver cancer diagnosis
Researchers have identified proteins that could be used to improve the diagnosis of hepatocellular carcinoma, the most common type of liver cancer.
Hepatocellular carcinoma causes about one million deaths each year and is especially frequent in Asia, especially in China, where it is the second most frequent fatal cancer. But the diagnostic methods and therapies are limited, which has prompted scientists to look for proteins inside the body that indicate the presence of the disease.
Fuchu He and colleagues have used a state-of-the-art technique called two-dimensional difference gel electrophoresis to look for proteins whose copies are either increased or decreased in patients with hepatocellular carcinoma. Among the many proteins they found, two proteins were validated as novel potential markers of hepatocellular carcinoma.
Article: “Proteome Analysis of Hepatocellular Carcinoma by Two-dimensional Difference Gel Electrophoresis,” by Wei Sun, Baocai Xing, Yi Sun, Xiaojuan Du, Min Lu, Chunyi Hao, Zhuang Lu, Wei Mi, Songfeng Wu, Handong Wei, Xue Gao, Yunping Zhu, Ying Jiang, Xiaohong Qian, and Fuchu He
MEDIA CONTACT: Fuchu He, Beijing Institute of Radiation Medicine, Beijing, China; tel: 8610-68177417; e-mail: hefc@nic.bmi.ac.cn
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Journal
Molecular & Cellular Proteomics