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Cysteine Sulfhydryls in Tau Display Unusual Hyperreactivity
Author(s) -
Lam YiLi,
Anand Malini,
Peterson Dylan,
Lew John
Publication year - 2021
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.2021.35.s1.01780
Subject(s) - cinnamaldehyde , chemistry , peptide , cysteine , in vitro , in vivo , biochemistry , biophysics , enzyme , biology , microbiology and biotechnology , catalysis
Pathological tau aggregation is one of the major hallmarks of Alzheimer's disease, for which there are no effective treatments thus far. We previously reported that cinnamaldehyde, in cinnamon, could inhibit tau aggregation in vitro by reacting with one or both cysteines in tau. Herein, we have investigated the reaction kinetics of the cysteines in tau and have found that cinnamaldehyde displays significant hyperreactivity towards both cysteines in tau compared to model sulfhydryl compounds as well as a short tau peptide corresponding to the sequence surrounding both cysteines. Further, the hyperreactivity is specific to cysteines in tau as opposed other sulfhydryl‐containing cellular proteins. Cinnamaldehyde displays several characteristics that make it favorable as a potential inhibitor of aggregation in vivo: it is both water and lipid soluble, brain‐permeable, non‐toxic, and inexpensive. The preferential targeting of tau is an additional favorable property of cinnamaldehyde as a potential Alzheimer's therapeutic or lead compound.