Genistein downregulates presenilin 1 and ubiquilin 1 expression

Abstract

Abstract. The aim of this study was to determine the effects of several food ingredients and chemical inhibitors on the expression of presenilin, a molecule involved in γ-secretase activity and the generation of amyloid-β peptide in Alzheimer's disease. Western blotting revealed the downregulation of presenilin 1 protein expression by stimulation with genistein in vitro, while the effects on presenilin 1 gene expression examined by reverse transcriptase-polymerase chain reaction (RT-PCR) were unaltered in Daudi cells. Genistein likely downregulates presenilin via the inhibition of ubiquilin 1 expression in lymphoid cells. Our findings provide new insights that may help to establish preventive strategies against Alzheimer's disease.

Potential Protective Mechanisms of S-equol, a Metabolite of Soy Isoflavone by the Gut Microbiome, on Cognitive Decline and Dementia

“…Major neuropathological hallmarks of AD involve protein aggregation as amyloid-β in extracellular plaques and phosphorylated tau in intracellular neurofibrillary tangles [ 106 ]. Several studies reported neuroprotective effects of genistein on amyloid-β-induced neurotoxicity and tau phosphorylation [ 107 , 108 , 109 , 110 , 111 , 112 ]. Compared to genistein, a few studies have investigated the effect of S-equol on amyloid-β-induced neurotoxicity and tau-phosphorylation.…”

“…Since genistein and S-equol are not only structurally similar but also possess similar affinity to ERβ, effects and mechanisms of genistein on amyloid-β and tau phosphorylation may, to some extent, apply to those of S-equol. Okamura et al, using the human cell lines Daudi, Jurkat, U937, and K562, showed that genistein decreased the generation of amyloid-β by downregulation of the transmembrane protein presenilin 1, which is involved in the amyloid precursor protein (APP) cleavage [ 107 ]. Li et al, using female ob/ob and control mice fed with a standard diet or diet with genistein for 4 weeks, showed that genistein reduced amyloid-β deposition and the level of hyper-phosphorylated tau in the brain and that genistein increased the expression levels of the neurotrophic factors, nerve growth factor, and brain-derived neurotrophic factors [ 112 ].…”

Emerging Signal Regulating Potential of Genistein Against Alzheimer’s Disease: A Promising Molecule of Interest

“…AD-linked ubiquilin-1 controls proteasomal degradation of proteins, comprising presenilin (Zhang and Saunders, 2009). Genistein can cause decreased Aβ generation by downregulation of the transmembrane protein presenilin which is found to be involved in the APP cleavage (Matsuda et al, 2011). On the other hand, in the lymphoid cells, genistein exerts an inhibitory action on the protein ubiquilin 1 which usually can cause stabilization of the presenilin (Matsuda et al, 2011).…”

“…Genistein can cause decreased Aβ generation by downregulation of the transmembrane protein presenilin which is found to be involved in the APP cleavage (Matsuda et al, 2011). On the other hand, in the lymphoid cells, genistein exerts an inhibitory action on the protein ubiquilin 1 which usually can cause stabilization of the presenilin (Matsuda et al, 2011). Though the molecular mechanisms by which ubiquilin 1 is controlled have not yet been recognized, this result may aid to develop defensive approaches against AD.…”