History of the treatment of psoriasis

Critical Cysteine Residues of Kelch-Like ECH-Associated Protein 1 in Arsenic Sensing and Suppression of Nuclear Factor Erythroid 2-Related Factor 2

“…In particular, millions of people are at risk of drinking arseniccontaminated water, presenting a major public health concern worldwide (Gomez-Caminero et al, 2001;NRC, 2001). On the other hand, arsenic has been used effectively as a therapeutic agent in the treatment of leukemia, psoriasis, and sleeping sickness (Farber, 1992;Carter and Fairlamb, 1993;Wang and Chen, 2008). The pleiotropic nature of arsenic effects implicates multiple protein targets of the soft metal in its diverse biological effects, few of which have been identified.…”

Inhibition of NF-κB Activation by Arsenite through Reaction with a Critical Cysteine in the Activation Loop of IκB Kinase

“…Despite its toxicity, potassium arsenite (Fowler's solution) has been used in the treatment of psoriasis, a chronic inflammatory disease of the skin (2). However, treatment with Fowler's solution frequently results in malignant skin lesions and hyperkeratosis, as well as liver fibrosis and other pathologies (3)(4)(5).…”

“…1 Incubation of cultured cells with sub-lethal doses of arsenite resulted in activation of all three major MAPK pathways, ERK, JNK, and p38 (8). 2 The activation of MAPKs by arsenite may explain its ability to act as a tumor promoter (1,3,7). Indeed, other tumor promoters, such as phorbol esters, also lead to MAPK activation.…”

Arsenic Induces NAD(P)H-quinone Oxidoreductase I by Disrupting the Nrf2·Keap1·Cul3 Complex and Recruiting Nrf2·Maf to the Antioxidant Response Element Enhancer

“…Whereas acute exposure to inorganic arsenic in humans results in cardiac failure, peripheral neuropathy, anemia, leucopenia, and death, chronic arsenic exposure can cause a range of cancers (particularly of the skin, lung, bladder, and liver) as well as liver injury, neuropathy, cardiovascular lesions, ovarian dysfunction, aberrant embryo development, and postnatal growth retardation (4, 6 -10). Interestingly, arsenic-containing compounds have proven to be effective as therapeutic agents in treating cancer such as leukemia (11), chronic inflammatory disease such as psoriasis (12), and parasitic infection such as sleeping sickness (13,14). Although chemical interaction with protein thiol groups and generation of reactive oxygen species have been implicated in the actions of arsenic, the exact molecular targets and signaling pathways that account for most of the biological effects of arsenic remain unknown.…”