IMR Press / JIN / Volume 22 / Issue 6 / DOI: 10.31083/j.jin2206145
Open Access Opinion
A Missing Origin of the Tau Protein Aggregation Pathway Triggered by Thermal and Biological Forces
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1 Center for Photochemical Sciences, Department of Chemistry, Bowling Green State University, Bowling Green, OH 43403, USA
*Correspondence: (H. Peter Lu)
J. Integr. Neurosci. 2023, 22(6), 145;
Submitted: 11 July 2023 | Revised: 11 August 2023 | Accepted: 15 August 2023 | Published: 23 October 2023
(This article belongs to the Special Issue Tau Functions and Dysfunctions in Brain Disorders)
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Fluctuations in mechanical force vectors within living cells can substantially influence the behavior and functions of proteins. Tau protein can spontaneously be raptured and entangled in refolding under picoNewton compressive forces that are biologically available in a living cell: a hidden aggregation pathway due to stress and crowding. Our findings were achieved through a customized modification of atomic force microscopy (AFM) for single-molecule manipulation. This previously hidden phenomenon of proteins rupturing collectively while subsequently and spontaneously refolding into a complex entangled conformation, distinct from the Tau protein’s folded or unfolded states, could potentially explain the early-event initiation of the aggregation of the Tau protein seen in various neurodegenerative diseases. This article introduces our recent discovery of the missing Tau protein property that is of significant relevance to the Tau protein and neurodegenerative disease research and medical treatment, aiming to stimulate the collective observation and a new perspective on the Tau aggregation mechanism and disease mechanism studies.

Tau protein
mechanical force
neuronal degenerate diseases
Ohio Eminent Scholar Endowment
Fig. 1.
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