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  • BUNINA BODIES  (1)
  • CHROMOGRANIN PEPTIDES  (1)
  • Patch clamp  (1)
  • 1
    Keywords: IN-VIVO ; GENE ; ALZHEIMERS-DISEASE ; IMMUNOREACTIVITY ; FRONTOTEMPORAL DEMENTIA ; CEREBROSPINAL-FLUID BIOMARKERS ; BUNINA BODIES ; CHROMOGRANIN PEPTIDES ; ALS PATIENTS ; EL-ESCORIAL
    Abstract: BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal disorder of the motor neuron system with poor prognosis and marginal therapeutic options. Current clinical diagnostic criteria are based on electrophysiological examination and exclusion of other ALS-mimicking conditions. Neuroprotective treatments are, however, most promising in early disease stages. Identification of disease-specific CSF biomarkers and associated biochemical pathways is therefore most relevant to monitor disease progression, response to neuroprotective agents and to enable early inclusion of patients into clinical trials. METHODS AND FINDINGS: CSF from 35 patients with ALS diagnosed according to the revised El Escorial criteria and 23 age-matched controls was processed using paramagnetic bead chromatography for protein isolation and subsequently analyzed by MALDI-TOF mass spectrometry. CSF protein profiles were integrated into a Random Forest model constructed from 153 mass peaks. After reducing this peak set to the top 25%, a classifier was built which enabled prediction of ALS with high accuracy, sensitivity and specificity. Further analysis of the identified peptides resulted in a panel of five highly sensitive ALS biomarkers. Upregulation of secreted phosphoprotein 1 in ALS-CSF samples was confirmed by univariate analysis of ELISA and mass spectrometry data. Further quantitative validation of the five biomarkers was achieved in an 80-plex Multiple Reaction Monitoring mass spectrometry assay. CONCLUSIONS: ALS classification based on the CSF biomarker panel proposed in this study could become a valuable predictive tool for early clinical risk stratification. Of the numerous CSF proteins identified, many have putative roles in ALS-related metabolic processes, particularly in chromogranin-mediated secretion signaling pathways. While a stand-alone clinical application of this classifier will only be possible after further validation and a multicenter trial, it could be readily used to complement current ALS diagnostics and might also provide new insights into the pathomechanisms of this disease in the future.
    Type of Publication: Journal article published
    PubMed ID: 22970211
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  • 2
    ISSN: 1432-1351
    Keywords: Area postrema ; Rabbit ; Patch clamp ; Glutamate-receptor ; GABA-receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Using the patch-clamp technique in combination with sliced tissue preparation the membrane properties of newborn rabbit area postrema neurons were investigated. The neurons responded upon depolarization with a fast Na +-current followed by an inactivating and non-inactivating K +-current. GABA-activated currents were investigated resulting in a large Cl--conductance, indicating the expression of GABAA-receptors. The expression of glutamate receptor mRNA was studied by in situ hybridization and electrophysiological measurements of these receptors by means of the patch-clamp technique. As a main result it was found that ionotropic glutamate receptors in the area postrema are composed of “flop” variants of the GluA-, GluB- and GluC-subunits.
    Type of Medium: Electronic Resource
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