Authors: (Zhou Wu, Hiroshi Nakanishi, Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Fukuoka, Japan, and others)
Abstract: Tumor necrosis factor-α (TNF-α) has many physiological roles in
homeostasis, including the regulation of cell survival and apoptosis. In
addition, TNF-α plays a central role in the inflammation and innate
immunity following its overproduction. Macrophages and microglia are
widely accepted as major TNF-α producers as well as responders in
systemic inflammation and the subsequent neuroinflammation,
respectively. Because TNF-α plays a crucial role in the inflammatory
responses and innate immunity, it is an attractive therapeutic target for
the treatment of patients with rheumatoid arthritis, atherosclerosis and
Alzheimer's disease. There is increasing evidence that cathepsin B
(CatB), a typical lysosomal cysteine protease, is involved in TNF-α
signaling and innate immunity. We herein describe the roles of CatB in
TNF-α signaling-mediated apoptosis, inflammation and innate immunity. In addition, we discuss a possible therapeutic usefulness of
CatB inhibitors on the treatment for inflammatory diseases.
