Wnt/PCP signalling cascade disruption by JNK inhibition as a potential mechanism underlying the teratogenic effects of potato glycoalkaloids

摘要

It is hypothesised that the inhibition of the non-canonical Wnt/PCP intracellular signalling cascade by potato glycoalkaloids, alpha-solanine and alpha-chaconine, results in an increased risk of neural tube defects (NTDs). One very prominent intracellular signalling pathway with substantial implications in the development and closure of the neural tube is the Wnt/PCP pathway. Experimental inhibition of this results in NTDs. A vital element of this signalling cascade is JNK, which controls the transcription of DNA, which controls cell polarity and directional cell migration. JNK inhibition also results in NTDs experimentally. Through their use in cancer research, alpha-solanine and alpha-chaconine were found to inhibit metastasis by inhibiting JNK, among other intracellular signalling molecules. Thus, this shows that potato glycoalkaloids increase the likelihood of causing NTDs by inhibiting the proper functioning of JNK in the Wnt/PCP pathway, resulting in defective neural tube closure.