Traumatic brain injury and the pathways to cerebral tau accumulation

Abstract

Tau is a protein that has received national mainstream recognition for its potential negative impact to the brain. This review succinctly provides information on the structure of tau and its normal physiological functions, including in hibernation and changes throughout the estrus cycle. There are many pathways involved in phosphorylating tau including diabetes, stroke, Alzheimer's disease (AD), brain injury, aging, and drug use. The common mechanisms for these processes are put into context with changes observed in mild and repetitive mild traumatic brain injury (TBI). The phosphorylation of tau is a part of the progression to pathology, but the ability for tau to aggregate and propagate is also addressed. Summarizing both the functional and dysfunctional roles of tau can help advance our understanding of this complex protein, improve our care for individuals with a history of TBI, and lead to development of therapeutic interventions to prevent or reverse tau-mediated neurodegeneration.

Keywords: brain pathology; neurodegeneration; repetitive head injury; tau; traumatic brain injury.

Figure 1

Diagram of the genetic splicing that produces Tau isoforms (A) and the enzymes involved in physiological regulation of tau phosphorylation (B). Note that phosphorylation of tau at T231 is responsible for trans to cis conformational change.

Figure 2

Schematic diagram of the many posttranslational modifications of tau that increase or decrease tau aggregation.

Figure 3

All pathways to tau phosphorylation from numerous diseases and exposures based on literature. It is important to note that those in red are all pathway elements initiated by traumatic brain injury.

Figure 4

Diagram of Tau aggregation and propagation between cells.