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Proteomics in neurodegeneration – disease driven approaches

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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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