Abstract
It is essential to characterize the proteome of various regions of human brain because most, if not all, neurodegenerative diseases are region-specific. Here we report an in-depth proteomics identification of proteins extracted from the frontal cortex, a region playing a critical role in cognitive function. The integrated proteomics analytical flow consisted of biochemical fractionation, strong cation exchange chromatography, reverse phase liquid chromatography, and MALDI-TOF/TOF mass spectrometric analysis. In total, 812 proteins were confidently identified with two or more peptides. These proteins demonstrated diverse isoelectric points and molecular weights and are involved in several molecular functions, including protein binding, catalytic activity, transport, structure, and signal transduction. A number of proteins known to be associated with neurodegenerative diseases were also identified. Detailed characterization of these proteins will supply the necessary information to appropriately interpret proteins associated with aging and/or age-related neurodegenerative diseases. Finally 140 proteins found in the cortical proteome were present in the proteome of cerebrospinal fluid, providing tissue-specific candidates for biomarker discovery in body fluid.
Highlights
It is essential to characterize the proteome of various regions of human brain because most, if not all, neurodegenerative diseases are region-specific
Other parallel proteomics studies on human temporal lobe tissue include two-dimensional electrophoresis separation coupled with analysis by a MALDI-TOF/TOF mass spectrometer, which identified 375 proteins [12], and a shotgun proteomics approach, consisting of strong cation exchange chromatography (SCX) and reverse phase (RP) LC for peptide separation, and a threedimensional ion trap mass spectrometer (LCQ), which identified 209 proteins [13]
The tryptic digests of the proteins in each fraction were further separated with SCX and RP LC before analysis with MALDI-TOF/TOF
Summary
It is essential to characterize the proteome of various regions of human brain because most, if not all, neurodegenerative diseases are region-specific. We investigated the proteome of human frontal cortex, a region involved in many neurodegenerative diseases with cognitive dysfunction. Proteins signifying disease progression are being actively investigated, it is important to make proteome data about human cortex, which is largely unknown, available to the investigators in the field.
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