HYBRID EVENT: You can participate in person at Paris, France or Virtually from your home or work.
Lecaille, Speaker at Dermatology Conferences
Tours university, France
Title : Modulation of the expression and activity of cathepsin S in reconstructed human skin by neohesperidin dihydrochalcone


Dysregulation of cathepsin S (Cat S), a cysteine protease involved in extracellular-matrix and basement membrane (BM) degradation, is a concomitant feature of several inflammatory skin diseases. Therefore, Cat S has been suggested as a potential therapeutic target. Flavonoids, which were identified as regulatory molecules of various proteolytic enzymes, exert beneficial effects on skin epidermis. Herein, thirteen flavonoid compounds were screened in vitro and in silico and neohesperidin dihydrochalcone (NHDC) was identified as a potent, competitive, and selective inhibitor (Ki=8±1 µM) of Cat S. Furthermore, Cat S-dependent hydrolysis of nidogen-1, a keystone protein of BM architecture, as well elastin, collagens I and IV was impaired by NHDC, while both expression and activity of Cat S were significantly reduced in NHDC-treated human keratinocytes. Moreover, a reconstructed human skin model showed a significant decrease of both mRNA and protein levels of Cat S after NHDC treatment. Conversely, the expression of nidogen-1 was significantly increased. NHDC raised IL-10 expression, an anti-inflammatory cytokine, and mediated STAT3 signaling pathway, which in turn dampened Cat S expression. Our findings support that NHDC may represent a valuable scaffold for structural improvement and development of Cat S inhibitors to preserve the matrix integrity and favor skin homeostasis during inflammatory events.

Audience Take Away Notes:

  • This research could be use by other institutions to expand their research or teaching
  • These results could provide practical solution to reduce cathepsin S overexpression and/or activity during skin disorders
  • This research provides informations to assist in the design of new cathepsin S inhibitors


Fabien Lecaille is a Professor of Biochemistry at Tours University, France. He obtained his Ph.D. in 2000 at the Francois Rabelais University in Tours (France) under the guidance of Dr. Gilles Lalmanach. In 2001, he joined as a postdoctoral fellow the laboratory of Pr. Dieter Brömme at the Mount Sinai School of Medicine in New York city (USA). In 2002, he returned to academia at Tours University as a Lecturer, Associate Professor, and full Professor in 2022. His main interests are human papain-like cysteine proteases and their roles in health and disease. He is the author of 68 publications.