Current Proteomics
ISSN: 1570-1646
Current Proteomics
Volume 3 Number 2, July 2006
Contents
Causes and Diagnosis of Alzheimer’s Disease:
A Proteomics Approach Pp. 81-112
A. Poljak, P. Sachdev and G.A. Smythe
[Abstract]
Phospho-Specific Antibodies: A Versatile Tool
for Phosphoproteomic Studies Pp. 113-117
C.E. Sykes and P.O. Vacratsis
[Abstract]
Bioinformatic Standards for Proteomics-Oriented
Mass Spectrometry Pp. 119-128
A. Droit, J. Fillon, J. Morissette and G.G. Poirier
[Abstract]
A Missed Proteome in Living Organisms: A Hyppo
System Pp. 129-146
S.-Y. Seong
[Abstract]
Abstracts
[Back to top]
Causes and Diagnosis of Alzheimer’s Disease:
A Proteomics Approach
A. Poljak, P. Sachdev and G.A. Smythe
Proteomics has become a powerful tool facilitating hypothesis-driven
exploration of disease states as well as offering a global
approach which can uncover potentially important, though unexpected
links to disease etiology. Despite many recent advances, the
pathophysiological basis of Alzheimer’s disease is incompletely
understood. Alzheimer’s dementia almost certainly results
from a constellation of cellular changes, with considerable
interplay between multiple genetic and environmental factors.
As a multifactorial disease, it is an ideal candidate for
a proteomics approach which offers a broad spectrum view of
changes to protein expression. The use of proteomics in the
study of Alzheimer’s dementia is in its early days.
However, its importance as an approach to the study of this
disease has been recognized by a considerable number of review
papers on this topic. This review summarises the advances
that proteomics has so far offered to understanding the basis
of Alzheimer’s pathology. Further, the use of proteomics
to explore potential biomarkers of Alzheimer’s pathology
which might be of clinical or diagnostic use, will be addressed.
[Back to top]
Phospho-Specific Antibodies: A Versatile Tool
for Phosphoproteomic Studies
C.E. Sykes and P.O. Vacratsis
Protein phosphorylation, a reversible post-translational
modification, has been long identified as a critical regulator
in a growing number of cellular processes. Most notably, phosphorylation
has been implicated in the signal transduction pathways regulating
the cell cycle, cellular proliferation, differentiation, and
gene expression events. The ubiquitous nature of phosphorylation
as a control mechanism has led to the study of phosphoproteomics.
However, lack of univer-sally employed strategies in the enrichment,
identification, and characterization of phosphoproteins has
hindered the fea-sibility of elucidating a complete phosphoproteome.
Currently, antibodies that recognize either a single phosphorylated
amino acid residue or an entire phospho-specific motif are
available. The ability to utilize these antibodies both as
functional groups for affinity chromatography and probes in
immunodetection procedures makes them a versatile option in
phosphoproteomic research. In this article, the procedures
commonly used for phosphoproteomic analysis will be reviewed,
with a major focus on present developments and future challenges
using phosphospecific antibodies for phos-phoproteome explorations.
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Bioinformatic Standards for Proteomics-Oriented
Mass Spectrometry
A. Droit, J. Fillon, J. Morissette and G.G. Poirier
A major goal of proteomics is the complete description
of all the proteins present in cells, tissues and biological
fluids. The method of choice for identifying and characterizing
proteins for such purposes is protease digestion coupled with
mass spectrometry (MS) and subsequent protein sequence database
searching. New software tools to increase the sensitivity
and specificity of MS based protein identification and methods
for evaluating the validity of the peptide-mass spectrum matches
have been developed and existing software has generally been
improved. However, with the ongoing rapid increase in both
volume and fragmentation of publicly available MS protein
data, the development and adoption of data standards has become
pivotal to the realization of integrated systems biology investigations.
Unfortunately, the native data standards used by each type
of mass spectrometers, each database search engine, and each
public database currently differ. The diverse, nontransparent
nature of the proprietary data structures complicates the
necessary data integration and data comparison across experiments.
To overcome this problem, data standards have been developed
through the extensible markup language (XML). To date, the
most comprehensive standardization attempt has been concomitantly
conducted by the Institute for Systems Biology (mzXML, PepXML,
ProtXML) and the Proteomics Standard Initiative (mzData, PSI-MI).
Their standards eliminate the need to support multiple input
formats and significantly facilitate the exchange and publication
of MS-based proteomic data. In this article, we also discuss
the standards used for biological proteomic data representation
in order to facilitate interpretation and dissemination of
research results.
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A Missed Proteome in Living Organisms: A
Hyppo System
S.-Y. Seong
Living organisms are composed of millions different kinds
of molecules. Both hydrophilic and hydrophobic molecules make
up cells and tissues. However, in healthy tissues, hydrophobic
portions (hyppos) are seldom exposed on the surface of the
biological molecules and supramolecular organization. Since
the water-insoluble molecules could form non-productive and
even toxic aggregates in aqueous body fluid, they have the
potential to disturb homeostasis of living organisms. It looks
like living organisms have expended metabolic energy to verify
the water-solubility of biological molecules in extracellular
spaces and within the cells. I suggest that the network of
proteins and cells responsible for handling water-insoluble
molecules can be understood in a unified model, “a hyppo-handling
system (HHS)”. It appears to have evolved to detect,
quench and remove water-insoluble molecules or molecular complexes
that have exposed hyppos. The hyppos could become exposed
on biological molecules in various ways, like through denaturation,
chemical modification, and digestion by bacterial enzymes.
When the quenching/removing system is not sufficient to hide
or get rid of hyppos, the innate immune system could be activated
to accelerate removal of hyppos. It might help us understand
why many innate immune receptors are activated by damage-associated
molecular patterns as well as pathogen-associated molecular
patterns. The ancient HHS appears to have evolved into a well
organized innate immune system in higher eukaryotes to maintain
homeostasis when disturbed by water-insoluble molecules. Comprehension
of this process could broaden our understanding of various
immune-mediated pathogenesis by infection, autoimmunity, allergies,
atherosclerosis, diabetes and neurodegenerative disease like
Alzheimer’s disease.
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