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Protein biomarkers of amyotrophic lateral sclerosis: mass spectrometry‐based characterization of transthyretin
Author(s) -
Kolarcik Christi Lynn,
Darko Samuel W,
Bowser Robert
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a25-b
Subject(s) - transthyretin , amyotrophic lateral sclerosis , biomarker , proteomics , medicine , disease , neurodegeneration , population , pathology , chemistry , biochemistry , gene , environmental health
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease and is characterized by the progressive degeneration and death of motor neurons. Currently, established and objective molecular markers that allow for the diagnosis and monitoring of ALS are lacking. Recently, we have identified a panel of protein biomarkers for ALS using mass spectrometry‐based proteomics. One potential biomarker, transthyretin (TTR), was found to be decreased in the cerebrospinal fluid of ALS patients when compared to control subjects. We have identified specific post‐translational modifications of the TTR protein that are altered in ALS patients. Specifically, TTR adducts with cysteine (TTR‐Cys) or cysteinylglycine (TTR‐CysGly) are reduced in the ALS population and correlate with disease progression. However, ELISA specific for TTR showed no significant change in overall TTR protein levels suggesting that altered post‐translational protein modifications as opposed to total protein levels are important. We are now determining if these same TTR alterations occur within the blood plasma of ALS patients. We will also correlate the presence of TTR abnormalities to specific sub‐populations of ALS patients. Sources of research support: NIH grant ES013469 (RB) and NIH T32 EB001026 (CK)