**Abstract**

Amyloid fibrils are misfolded proteins, which are often associated with various neurodegenerative diseases such as Alzheimer's. The amount of hydrogen sulfide (H2S) is known to be reduced in the brain tissue of people diagnosed with Alzheimer's disease relative to that of healthy individuals. Hen Egg-White Lysozyme (HEWL) forms typical β-sheet-rich fibrils during 70 minutes at low pH and high temperatures. These results are consistent with the ThT findings that β-sheets structure is also present in myoglobin (Mb), and hemoglobin (Hb) in the presence of 45% TFE. The addition of H2S in the process completely inhibits the formation of amyloid fibrils in HEWL, Mb, and Hb as revealed by several spectroscopic techniques. Non-resonance Raman bands corresponding to disulfide (RSSR) vibrational modes in the 550-500 cm-1 spectral range decreases in intensity and is accompanied by the appearance of a new 490 cm-1 band assigned to the trisulfide group (RSSSR). Intrinsic tryptophan fluorescence shows a partial denaturation of HEWL containing trisulfide bonds. Overall, the Mb and Hb result ties excellent with the HEWL data showing that the presence of H2S during these proteins fibrillation processes protects the α-helical protein structures, preventing the formation of amyloids in these different proteins moieties.

**Keywords:** hydrogen sulfide, amyloid fibril, protein aggregates, lysozyme, myoglobin, hemoglobin, Raman spectroscopy, ultraviolet Raman spectroscopy, unordered protein, disulfide, trisulfide

<sup>1</sup> Materials in this chapter related to the lysozyme fibrillation and its inhibition by H2S, including text and figures was previously published in Journal of Physical Chemistry. 2015;119:1265-1274. PMID: 2554579. The direct link to the article is https://pubs.acs.org/doi/10.1021/jp508471v. Any further permissions related to the related material should be directed to the ACS.
