Neuroproteomics

What is Neuroproteomics?

It has been proposed by Marc Wilkins in 1994 that the overall protein content expressed by a genome, or a cell, or tissue under specific physiological conditions are named as proteome, which derives from the combination of the words “protein” and “genome”. Later in 1995, proteomics was coined which generally refers to the large-scale analysis of protein composition, structure, and function based on proteome unit. Neuroproteomics is a part of proteomics that studies complex proteomes in the nervous system. Neuroproteomics serves as a refined tool for the research of the expression, function, and molecular mechanisms of proteins in the nervous system.

Applications of Neuroproteomics

Neuroproteomics is primarily divided into four categories, expression neuroproteomics, functional neuroproteomics, clinical neuroproteomics, and neuroproteomic informatics. It can not only provide the material basis for neurological activities, but also provide the theoretical basis and solutions for the elucidation and conqueration of neurological disease mechanisms. A series of "disease-related protein molecules" can be identified through the comparative neuroproteomics analysis between normal and neurological disease individuals. These molecules further serve as biomarkers for early diagnosis and as targets for new therapy development. Additionally, neuroproteomics can also address:

1. The entire protein expression profiling of organelle, a cell, or a certain tissue under specific physiological or pathological conditions.
2. Analyze and characterize the post-translational modifications of these profiled proteins, such as glycosylation, ubiquitination, phosphorylation/dephosphorylation, etc.
3. Identify the neurological proteome alterations in composition and function as with aging, the disease progresses, genetic factors, environmental changes.
4. Explore the specific mechanisms of drug addictions and neurological diseases, especially psychiatric diseases.
5. Other applications such as subcellular fractionation, brain injuries, neuritis, The Human Proteome Organization-Brain Proteome Project.

Fig.2 The goal of clinical neuroproteomics research is ultimate to improve patient care. (Sjödin, 2012)

Research Techniques for Neuroproteomics

1. 2-dimensional electrophoresis (2-D electrophoresis)

2D-polyacrylamide gel electrophoresis is a powerful technique for protein separations, which can fractionate hundreds to thousands of proteins in one experiment with high resolution according to the different isoelectric points and molecular weight. Other techniques, such as 2D-fluorescence gel electrophoresis, 2D-capillary electrophoresis, liquid chromatography, are now also widely chosen for protein separation.

2. Mass spectrometry (MS)

MS is another important technique for neuroproteomics research, which is used for the identification of the separated proteins after proteolytic digestion. Commonly used MS techniques are Matrix-assisted Laser Desorption Ionization time-of-flight Mass Spectrometry (MALDI-TOF-MS) and Electrospray Mass Spectrometry (ESI-MS).

3. Protein arrays

In neuroproteomics, protein arrays usually are utilized for screening protein interactions and identifying protein modifications in nervous systems.

4. Other important techniques

A range of techniques and methods are also useful in neuroproteomics analysis, which mainly includes but is not limited to analytical ultracentrifugation, western blots, surface plasmon resonance, circular dichroism.

Fig.3 Flow of a prototypical Ms-based neuroproteomics experiment. (Bayés, 2009)

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References

1. Sjödin, M.O. Advances for Biomarker Discovery in Neuroproteomics using Mass Spectrometry: From Method Development to Clinical Application (Doctoral dissertation, Acta Universitatis Upsaliensis). 2012.
2. Bayés, A.; Grant, S.G. Neuroproteomics: understanding the molecular organization and complexity of the brain. Nature Reviews Neuroscience. 2009, 10(9): 635-646.