First, UPS impairment leads to the dysregulation of gene expression by reducing the degradation of transcriptional factors, e.g., NF-κB, HIF-1α, NFAT, etc., which contributes to the dysregulation of neurodegenerative disease-associated proteins, e.g., BACE1, RCAN1, TMP21, etc. (Sun et al., 2006; Liu et al., 2011; Ly et al., 2013; Wu and Song, 2013; Wu et al., 2015). Here, BACE1 is linked to neurodegenerative disease.