Our study demonstrates that NWL inhibitors are 1) non-toxic, but non-selective, strong Casp6 inhibitors in vitro, in colon cancer cells, and in primary CNS human neurons, 2) protective against Casp6-mediated neuritic degeneration in serum-deprived or APPWT expressing human neurons, 3) blood-brain barrier permeable, and 4) reversing episodic memory impairments in transgenic Casp6 mice. The gene discussed is CASP6; the disease is malignant colon neoplasm.