Peptidomics and traumatic brain injury: biomarker utilities for a theragnostic approach

Abstract The pathobiology of tau protein in traumatic brain injury (TBI) has spiked a great interest due to its role in existing neurodegenerative diseases and aging. Tau supports microtubule structural stability of axons and is altered in neurodegeneration, a condition known as tauopathies. Tau dissociates from the microtubules and aggregates into oligomers and forms neurofibrillary tangles. These tangles are subject to aggregation over time and lead to plaque leading to major diseases such as Alzheimer’s disease and Parkinson’s disease. Tau proteins are also subjected to posttranslational modifications (PTM), which exacerbate their detachment and oligomerization. Tau proteolysis into low ( 10K) molecular weight (LMW and HMW) fragments is a critical driver of tauopathy. HMW tau proteolytic fragments have been characterized in patients with different tauopathies, while LMW tauopathy peptides (peptidome) following TBI needs further characterization. Using peptidomics in TBI is a demanding and novel way of classifying tau peptides. Identification of LMW and HMW peptides, along with analysis of tau peptidome in the TBI context, might help reveal the simultaneous release of LMW tau proteolytic peptides, which could have diagnostic and therapeutic biomarker utilities, emphasizing the suppression of tau proteolysis as a target.