Molecular and Therapeutic Targets of Genistein in Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is a devastating brain disorder characterized by an increased level of amyloid-beta (Aβ) peptide deposition and neuronal cell death leading to an impairment of learning and thinking skills. The Aβ deposition is a key factor in senile plaques of the AD brain which cause the elevation of intracellular calcium ions and the production of formidable free radicals, both of which greatly contribute to the AD-associated cascade, leading to unstoppable neuronal loss in the hippocampal region of the brain. Natural products are currently considered as an alternative strategy for the discovery of novel multipotent drugs against AD. They include the naturally occurring dietary soy isoflavone genistein which has been recognized to possess several health-promoting effects. Genistein has been mainly focused because of its potential on amelioration of Aβ-induced impairment and its antioxidant capacity to scavenge the free radicals produced in AD. It can also directly interact with the targeted signaling proteins and stabilize their activity to prevent AD. An improved understanding of the direct interactions between genistein and target proteins would contribute to the further development of AD treatment. This review mainly focuses on molecular targets and the therapeutic effects regulated by genistein, which has the ability to directly target the Aβ peptide and to control its activity involved in intracellular signaling pathways, which otherwise would lead to neuronal death in the hippocampal region of the AD brain.

Characterization of phenolic profile by LC‐ESI‐MS/MS and enzyme inhibitory activities of two wild edible garlic: Allium nigrum L. and Allium subhirsutum L.

“…Moreover, genistein, a known isoflavonoid, was observed for major flavonoid and quantified as 159.3 µg/g extract in A. subhirsutum . Genistein has neuroprotective effects against Aβ 1‐42 ‐induced rats and Aβ 25‐35 ‐induced cultured hippocampal neuronal cells via different mechanisms in searching for AD treatment (Devi, Shanmuganathan, Manayi, Nabavi, & Nabavi, ). In addition, rutin was determined in trace amounts in the extracts of A. nigrum and while kaempferol was second major flavonoid for A. nigrum , detected in trace amounts in A. subhirsutum extracts.…”

“…Extraction yield, the total phenolic, and total flavonoid contents of extracts are shown in neuronal cell lines and this agent displayed significant in vitro protective effect in a model of PD (Nie et al, 2002). Also, another in vivo research implied that EGCG alleviated biochemical changes, including enhanced AChE activity, oxidative stress, cytokines, of ethanol-treated rat pumps (Tiwari, Kuhad, & Chopra, 2010 (Devi, Shanmuganathan, Manayi, Nabavi, & Nabavi, 2017).…”

Genistein protects against amyloid‐beta‐induced toxicity in SH‐SY5Y cells by regulation of Akt and Tau phosphorylation

“…Natural compounds have gained attention in recent times as possible alternative strategies for prevention or treatment of AD, as they have shown to inhibit pathogenic pathways related to the disease development (Almeida, Alves, Sousa, Oliveira, & Silva, ; Costa et al, ; Frozza et al, ; Hoppe et al, 2013a,b; Hussain et al, ; Lakey‐Beitia, Berrocal, Rao, & Durant, ; Pasinetti, Wang, Ho, Zhao, & Dubner, ; Pinho, Ferreres, Valentão, & Andrade, ; Swaminathan & Jicha, ). Genistein has emerged as a potential drug that shows promising effects against the neuronal damage associated with Aβ peptide (de Oliveira, ; Devi et al, ). In order to further investigate the neuroprotective roles of this drug, we initially evaluated its effect on cell death triggered by the peptide exposure.…”

“…Genistein (4′,5,7‐trihydroxyisoflavone) is one of the major isoflavones present in soybeans and soy products and has received special attention for its potential neuroprotective effects in different experimental models of Aβ‐induced toxicity (de Oliveira, ; Devi, Shanmuganathan, Manayi, Nabavi, & Nabavi, ). It has been reported in previous in vitro studies that genistein protects against cell death (Bang et al, ; Vallés et al, ; Xu et al, ; You et al, ; Yu et al, ), improves oxidative stress damages (Janicki & Schupf, ; Vallés et al, ), inhibits synaptic toxicity (Wang et al, ; Xi et al, ), and prevents release of inflammatory mediators (Valles et al, ), thus, the events that are known to be induced by Aβ peptide.…”

The Role of Selected Bioactive Compounds in the Prevention of Alzheimer’s Disease

“…It reduces oxidative stress by inhibiting the synthesis of oxygen reactive species. Moreover, genistein protects mitochondria by increasing reduced-to-oxidized glutathione ratio and lowering 8-oxo-2 -deoxyguanosine, a marker of mitochondrial DNA damage [47]. It also prevents apoptosis by restricting caspase-3 activity and ameliorates inflammation through reduction in TNF-α and NF-κB levels.…”