Summary.
Proteins as a product from genetic information execute and determine how development, growth, aging and disease factors are orchestrated within the lifetime of an organism. Differential protein expression and/or modification are always context dependent i.e. they happen within a specific context of a tissue, organ, environmental situation and individual fate. Consequently, the function/dysfunction (in a certain disease) of a specific gene cannot be predicted comprehensively by its sequence only. Genetic information can only be understood when genes and proteins are analyzed in the context of the biological system and specific networks they are involved in. In regard to neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s disease (PD) many proteins are known for long years to be the cause or the consequence of the pathomechanism of the respective disease. The treatment of these neurodegenerative diseases represents a major challenge for the pharmaceutical industry, whereas the understanding of their pathogenesis is still in its infancy. With the development of several powerful techniques for proteome analysis it is now possible to investigate the expression of thousands of proteins in single cells, tissues or whole organisms at the same time. These developments opened new doors in medical sciences, and identification of cellular alterations associated with e.g. neurodegeneration will result in the identification of novel diagnostic as well as therapeutic targets.
In this review, general considerations and strategies of proteomics technologies, the advantages and challenges as well as the special needs for analyzing brain tissue in the context of AD and AD are described and summarized.
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Abbreviations
- 2D-PAGE:
-
two-dimensional polyacrylamide gelelectrophoresis
- Aβ:
-
amyloid β-protein
- AC:
-
affinity chromatography
- ACPI:
-
atmosphereic pressure chemical ionisation
- AD:
-
Alzheimer’s disease
- APP:
-
amyloid precursor protein
- BAC:
-
benzyldimethyl-n-hexadecylammonium chloride
- CDL-5:
-
CDC2-related protein kinase 5
- CE:
-
capillary electrophoresis
- CHAPS:
-
3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate hydrate
- CI:
-
chemical ionization
- CTAB:
-
Hexadecyltrimethylammonium bromide
- DIGE:
-
difference gel electrophoresis
- DRP-2:
-
dihydropyrimidinase-related protein-2
- DNPH:
-
2,4-nitrophenylhydrazine
- EI:
-
electron impact
- ESI:
-
electrospray ionization
- FAB:
-
fast atom bombardment
- GSKβ3:
-
glycogen synthase kinase 3β
- HPLC:
-
high performance liquid chromatography
- IEF:
-
isoelectric focusing
- IEX:
-
ionexchange chromatography
- LB:
-
Lewy body
- MALDI:
-
matrix assisted laser desorption/ionization
- mdLC:
-
multi dimesional liquid chromatography
- MIDAS:
-
multiple reaction monitoring initiated detection and sequencing
- mRNA:
-
messenger ribonucleinacid
- MS:
-
mass spectrometry
- MS/MS:
-
tandem mass spectrometry
- MuD-PIT:
-
multidimensional protein identification technology
- PD:
-
Parkinson’s disease
- PMF:
-
peptide mass fingerprint
- PTMs:
-
post-tramslational modifications
- PSD:
-
postsource decay
- PVDF:
-
polyvinylidene difluoride
- RPC:
-
reversed phase chromatography
- SDS:
-
sodiumdodecylsulfate
- SEC:
-
size-exclusion chromatography
- SELDI:
-
surface enhanced laser desorption/ionisation
- TOF:
-
time of flight
- TPI:
-
triose phosphate isomerise
- TRIS:
-
Tris(hydroxymethyl)aminomethane
- UCH-L1:
-
ubiquitin C-terminal hydrolase-L1
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Schulenborg, T., Schmidt, O., van Hall, A. et al. Proteomics in neurodegeneration – disease driven approaches. J Neural Transm 113, 1055–1073 (2006). https://doi.org/10.1007/s00702-006-0512-8
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DOI: https://doi.org/10.1007/s00702-006-0512-8