Synopsis

Hair is closely linked to feeling of health, wellbeing, and beauty, and is the ultimate tool of self-expression. Problems associated with hair growth and loss include: a reduction in follicle density; follicle miniaturisation resulting in weaker and finer hairs which break more easily; thinner hair fibres leading to feeling of reduced volume; slower hair growth; and excessive shedding. The human hair follicle is a regenerating biological system whose primary function is to produce a hair fibre. The hair growth cycle consists of 3 key phases: growth (anagen), regression (catagen) and rest (telogen), which occur continuously throughout the follicle lifetime. During catagen, the growing fibre produced in anagen becomes detached from the follicular matrix and is subsequently referred to as the ‘club fibre’. The club fibre eventually sheds from the follicle in a process termed exogen.
A multitude of underlying biological pathways and signalling molecules control the different phases of the human hair follicle cycle. The vast majority of hair biology research, spanning several decades, has focused on the hair growth cycle, whilst little attention has been devoted to studying the mechanisms involved in exogen. Understanding the factors that control exogen may shed light on routes to mitigate excessive hair shedding. Reports support the role of protease enzymes such as serine proteases in the mechanism of action during hair shedding. Retention of the club fibre in the follicle is thought to involved enzyme inhibitors such as plasminogen activator inhibitor type 2 [1] and tissue inhibitor of metalloprotease 3 [1].
We have confirmed expression of serine proteases around the human hair follicle, in addition to confirming protease activity in the material extracted from human club fibre bulbs. Furthermore, we have shown inhibition of protease activity in vitro in club fibre bulb extracts using known serine protease inhibitors. In this presentation we will aim to showcase the vital role these enzymes play during hair shedding, and how inhibition of excess levels offers a potential means for retention of club hairs, and consequently a reduction in excessive hair fall.

[1] Lavker RM, Risse B, Brown H, et al., Localization of plasminogen activator inhibitor type 2 (PAI-2) in hair and nail: implications for terminal differentiation [J]. Journal of Investigative Dermatology. 1998, 110;917–922.
[2] Higgins CA, Westgate GE, Jahoda CA. Modulation in proteolytic activity is identified as a hallmark of exogen by transcriptional profiling of hair follicles [J]. Journal of Investigative Dermatology. 2011, 131:2349–2357.