Preventing Neurodegenerative Diseases By Studying Proteins In The Brain

Main Category: Neurology / Neuroscience
Also Included In: Biology / Biochemistry;  Alzheimer's / Dementia;  Parkinson's Disease
Article Date: 06 Oct 2007 - 0:00 PDT

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Researchers report in the October 2007 issue of Molecular & Cellular Proteomics 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

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