The Role of Aldose Reductase and Oxidative Stress in Alopecia Areata

Alopecia areata (AA) is an autoimmune inflammatory condition that can present as "patchy" hair loss that can sometimes progress to a complete loss of scalp and body hair. Our understanding of the underlying mechanisms of AA pathogenesis are limited, and therapeutic options that bring lasting hair restoration are insufficient.

We have preliminary data showing that Aldose Reductase (AKR1B1) expression may be increased within outer root sheath keratinocytes within AA scalp tissue sections. AKR1B1 can be upregulated during cellular stress, and has various functions including roles in metabolism and in the reduction of oxidative stress-induced aldehydes, which can in turn influence important immune cell-regulatory pathways like NF-kB signaling.

Furthermore, oxidative stress, marked by excessive reactive oxygen species production, has been observed in autoimmune inflammatory diseases including AA. However, the role of AKR1B1 and its relationship to oxidative stress has not yet been explored in normal human hair follicle biology or in AA.

To address this, this project will utilise ex vivo human hair follicle organ culture, in vitro hair follicle cell culture models and clinical tissue samples to dissect the functional role of AKR1B1 and its relationship to oxidative stress in both healthy scalp hair follicles and in AA.