Human High Temperature Requirement Serine Protease A1 (HTRA1) Degrades Tau Protein Aggregates

A critical first step in finding the cure to any disease is determining the biological mechanisms that contribute to its pathology. This is no small task, but once understood researchers can begin to focus their energy on developing therapies to mitigate or promote activities related to the onset or prevention of the disease. Of course, determining what causes a disease is only half the battle. From there, an appropriate therapy needs to be developed that not only treats the condition, but also does minimal damage to other biological systems. In the case of neurodegenerative disorders such as Alzheimer's disease, a number of mechanisms have been discovered to be behind the symptoms, such as memory loss and decreased cognitive function. It has been determined that the accumulation and aggregation of misfolded proteins can significantly impede brain function, and are critical preconditions for the onset of a variety of neurological disorders. Specifically, aggregated tau fibrillar proteins are widely considered to be significant pathogens of conditions like AD. As such, finding ways to degrade these protein aggregations is essential if effective treatments for these diseases are to be found.

Since the high temperature requirement A (HTRA) family of serine proteases has been shown to play a key role in ATP-protein control, Tennstaedt et al. decided to look at how HTRA1 would impact the aggregation of tau proteins, especially since this potential therapy option for neural disorders has not received much attention in the medical research community. One of the ways this team measured the effectiveness of HTRA1 in cleaving aggregated proteins was to compare it to two other proteases known to have this effect: human calpain 1 and recombinant human capsase 3. For the latter, the researchers used Ac-DEVD-pNA provided by ATT Bioquest. By doing so, the team was able to assure itself on the reliability of the results they obtained, thanks to the Ac-DEVD-pNA's high integrity.

The results of the study indicated that HRTA1 can, in fact, play a significant role in breaking apart poorly formed or aggregated tau proteins, suggesting that it could have a potential role in any therapy being developed for neural disorders. By using quality materials such as Ac-DEVD-pNA, the team was able to confidently compare their results with what is already known, allowing for further reliability of their results. While a cure for the most serious neurodegenerative disorders is still far down the road, studies such as the one conducted by Tennstaed et al. show how the research community is getting closer every day, and with the quality of materials employed to study these mechanisms, it is reasonable to think that a day where a safe and effective treatment exists is right around the corner.

References

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1. Tennstaedt, Annette, et al. "Human high temperature requirement serine protease A1 (HTRA1) degrades tau protein aggregates." Journal of Biological Chemistry 287.25 (2012): 20931-20941.