Green Tea Epigallocatechin-3-gallate (EGCG) Targeting Protein Misfolding in Drug Discovery for Neurodegenerative Diseases

Abstract

The potential to treat neurodegenerative diseases (NDs) of the major bioactive compound of green tea, epigallocatechin-3-gallate (EGCG), is well documented. Numerous findings now suggest that EGCG targets protein misfolding and aggregation, a common cause and pathological mechanism in many NDs. Several studies have shown that EGCG interacts with misfolded proteins such as amyloid beta-peptide (Aβ), linked to Alzheimer’s disease (AD), and α-synuclein, linked to Parkinson’s disease (PD). To date, NDs constitute a serious public health problem, causing a financial burden for health care systems worldwide. Although current treatments provide symptomatic relief, they do not stop or even slow the progression of these devastating disorders. Therefore, there is an urgent need to develop effective drugs for these incurable ailments. It is expected that targeting protein misfolding can serve as a therapeutic strategy for many NDs since protein misfolding is a common cause of neurodegeneration. In this context, EGCG may offer great potential opportunities in drug discovery for NDs. Therefore, this review critically discusses the role of EGCG in NDs drug discovery and provides updated information on the scientific evidence that EGCG can potentially be used to treat many of these fatal brain disorders.

Myricetin Inhibits α‐Synuclein Amyloid Aggregation by Delaying the Liquid‐to‐Solid Phase Transition

“…Brazilin had a strong inhibitory effect on the aggregation of Aβ, remodeling Aβ amyloid fibrils by interaction with Aβ 17–42 pentamer [22] . In the past few decades, a subset of phenolic compounds, especially the polyphenols such as curcumin, myricetin, epigallocatechin gallate, hydroxycinnamic acids, rosmarinic acid, and ferulic acid, were reported to have strong anti‐aggregation effects on α‐Syn [26–36] . Interestingly, some compounds containing only one aromatic ring can inhibit α‐Syn aggregation [37] .…”

“…[22] In the past few decades, a subset of phenolic compounds, especially the polyphenols such as curcumin, myricetin, epigallocatechin gallate, hydroxycinnamic acids, rosmarinic acid, and ferulic acid, were reported to have strong anti-aggregation effects on α-Syn. [26][27][28][29][30][31][32][33][34][35][36] Interestingly, some compounds containing only one aromatic ring can inhibit α-Syn aggregation. [37] Due to the lack of structural information, the detailed mechanisms of α-Syn-phenolic compounds' interactions remain largely unclear.…”

EGCG Promotes FUS Condensate Formation in a Methylation-Dependent Manner

“…Several studies have demonstrated the role of green tea catechins in neuroprotection, with epigallocatechin gallate (EGCG) being widely studied because it constitutes 65% of all catechins in green tea [ 8 , 9 , 10 , 11 ]. The green tea catechins play a variety of roles in neuroprotection, such as exerting (i) anti-oxidative properties through radical scavenging and metal ion chelation [ 12 , 13 , 14 ], (ii) anti-apoptotic properties through the reduction in pro-apoptotic gene expression [ 15 ], (iii) anti-inflammatory properties through the inhibition of microglia activation [ 16 ], and (iv) anti-amyloidogenic properties through the remodeling of toxic aggregates [ 8 , 17 ]. The latter role of catechins in neuroprotection is of great interest as it counteracts the hallmark of NDs (formation of protein aggregates), which is thought to drive the process of neurodegeneration.…”

Selected Natural Products in Neuroprotective Strategies for Alzheimer’s Disease—A Non-Systematic Review

“…Some aggregated species might be neurotoxic and lead to neurodegeneration [67]. For this reason, targeting neuronal accumulation of α-synuclein is appealing as a promising approach to delaying the progression of AD [68,69].…”