1 research outputs found
An ATR–FTIR Sensor Unraveling the Drug Intervention of Methylene Blue, Congo Red, and Berberine on Human Tau and Aβ
Alzheimer’s
disease affects millions of human beings worldwide.
The disease progression is characterized by the formation of plaques
and neurofibrillary tangles in the brain, which are based on aggregation
processes of the Aβ peptide and tau protein. Today there is
no cure and even no <i>in vitro</i> assay available for
the identification of drug candidates, which provides direct information
concerning the protein secondary structure label-free. Therefore,
we developed an attenuated total reflection Fourier transform infrared
spectroscopy (ATR–FTIR) sensor, which uses surface bound antibodies
to immobilize a desired target protein. The secondary structure of
the protein can be evaluated based on the secondary structure sensitive
frequency of the amide I band. Direct information about the effect
of a drug candidate on the secondary structure distribution of the
total target protein fraction within the respective body fluid can
be detected by a frequency shift of the amide I band. Thereby, the
extent of the amide I shift is indicative for the compound efficiency.
The functionality of this approach was demonstrated by the quantification
of the effect of the drug candidate methylene blue on the pathogenic
misfolded tau protein as extracted from cerebrospinal fluid (CSF).
Methylene blue induces a shift from pathogenic folded β-sheet
dominated to the healthy monomeric state. A similar effect was observed
for congo red on pathogenic Aβ isoforms from CSF. In addition,
the effect of berberine on synthetic Aβ<sub>1–42</sub> is studied. Berberine seems to decelerate the aggregation process
of synthetic Aβ<sub>1–42</sub> peptides