TY - JOUR
T1 - Thioflavin T─a Reporter of Microviscosity in Protein Aggregation Process
T2 - The Study Case of α-Synuclein
AU - Rusakov, Konstantin
AU - El-Turabi, Aadil
AU - Reimer, Lasse
AU - Jensen, Poul Henning
AU - Hanczyc, Piotr
N1 - Publisher Copyright:
© 2024 The Authors. Published by American Chemical Society.
PY - 2024/6/27
Y1 - 2024/6/27
N2 - Thioflavin T (ThT) informed microviscosity changes can be used to monitor protein aggregation. Steady-state, time-resolved and lasing spectroscopy were used to detect transient states in α-synuclein - a protein associated with Parkinson’s disease. The major focus was on the nucleation phase, where conventional ThT fluorescence assay lacks appropriate sensitivity to detect early stage oligomers. Instead, lasing spectroscopy and lasing threshold parameters, in particular, were sensitive to detecting protein oligomers. Through lasing spectroscopy, a change in microviscosity correlating with the stages of protein aggregation was observed at two wavelengths 405 and 440 nm. The two wavelengths are associated with free dye molecules and β-sheet bound ThT molecules. This provides a perspective on elucidating the early formed protein aggregation, a critical aspect in understanding the pathogenesis of neurodegenerative diseases. The insights from the presented study shows the potential of using lasing spectroscopy as a sensitive tool in studying protein aggregation dynamics.
AB - Thioflavin T (ThT) informed microviscosity changes can be used to monitor protein aggregation. Steady-state, time-resolved and lasing spectroscopy were used to detect transient states in α-synuclein - a protein associated with Parkinson’s disease. The major focus was on the nucleation phase, where conventional ThT fluorescence assay lacks appropriate sensitivity to detect early stage oligomers. Instead, lasing spectroscopy and lasing threshold parameters, in particular, were sensitive to detecting protein oligomers. Through lasing spectroscopy, a change in microviscosity correlating with the stages of protein aggregation was observed at two wavelengths 405 and 440 nm. The two wavelengths are associated with free dye molecules and β-sheet bound ThT molecules. This provides a perspective on elucidating the early formed protein aggregation, a critical aspect in understanding the pathogenesis of neurodegenerative diseases. The insights from the presented study shows the potential of using lasing spectroscopy as a sensitive tool in studying protein aggregation dynamics.
UR - http://www.scopus.com/inward/record.url?scp=85196655562&partnerID=8YFLogxK
U2 - 10.1021/acs.jpclett.4c00699
DO - 10.1021/acs.jpclett.4c00699
M3 - Journal article
C2 - 38899873
AN - SCOPUS:85196655562
SN - 1948-7185
VL - 15
SP - 6685
EP - 6690
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
IS - 25
ER -