Lanthionine ketimine was recognized as a natural
metabolite as early as 1983 by Dorianno Cavallini, who published regarding its synthesis and chemical properties. Cavallini and others showed that lanthionine ketimine forms from alternative reactions of the
transsulfuration pathway enzyme
cystathionine-β-synthase, which normally condenses the
amino acids homocysteine and
serine to form
cystathionine. In an alternate pathway,
cysteine and
serine (or two equivalents of
cysteine) condense to form
lanthionine. The product of these transformations is lanthionine or cystathionine ketimine, It has been hypothesized, but not proved, that LANCL1 might catalyze formation of glutathione-lanthionine conjugates in a pathway leading to lanthionine ketimine. This
neurotrophic activity may occur through interaction of lanthionine ketimine with a protein called
collapsin response protein-2 (CRMP2, also known as dihydropyrimidinase-like protein-2 or DPYSL2). Normally CRMP2 functions to promote or inhibit neurite growth. Lanthionine ketimine interacts with CRMP2 in affinity
proteomics experiments and alters CRMP2 binding to other proteins in brain
lysate preparations. Beside its
neurotrophic effects, lanthionine ketimine and its ester LKE protect neurons against
oxidative stress and inhibit the activation of
microglia (brain macrophages) triggered by exposure to inflammatory
cytokines. Administration of LKE to the SOD1G93A
mouse model of the
motor neuron disease
amyotrophic lateral sclerosis (ALS), slows progression of
paralytic disease in this mouse. == Preparation ==