Figure 4. Synopsis of the 12/15Lipoxygenase pathway ion the context of Alzheimer's disease pathogenesis.
12/15Lipoxygenase (12/15LO) modulates Aβ production through the β-secretase by acting on the transcription factor Sp1. 12/15LO also modulates tau phosphorylation by acting on cdk5 and SAPK/JNK. As an end result, overexpression of 12/15 LO protein exacerbates the Alzheimer’ disease (AD) phenotype, while its knockout of pharmacological inhibition ameliorates synaptic dysfunction, memory impairments and cognitive decline in mouse models of the disease. Direct modulation of 12/15LO by PD146176 has demonstrated success in mitigating its effects on the AD phenotype.