From:  Neuroprotective insights into epigallocatechin gallate (EGCG) for neurodegenerative disorders

Neuroprotective mechanism: pathways and molecular targets for neural cell preservation

Mechanism category Specific actionMolecular targets/effectsNeuroprotective outcomeReferences
Antioxidant defenseDirect ROS/RNS scavengingO2, OH, ONOO−, H2O2Prevents oxidative damage to neurons and glial cells[25]
Antioxidant signalingNrf2/ARE pathway activationHO-1, NQO1, γ-GCS upregulationEnhanced cellular antioxidant capacity[26]
Mitochondrial protectionComplex I-IV activity enhancementElectron transport chain efficiencyImproved neuronal energy metabolism[27]
Membrane stabilizationPhospholipid organizationMembrane fluidity and integrityEnhanced synaptic function and plasticity[28]
Anti-inflammatoryMicroglial activation suppressionTNF-α, IL-1β, IL-6 reductionDecreased neuroinflammation[29]
Protein aggregationAmyloid-β fibril preventionDirect binding to Aβ monomersReduced amyloid plaque formation[30]
Protein homeostasisα-Synuclein aggregation inhibitionα-Syn oligomer disruptionPrevention of Lewy body formation[31]
Apoptosis controlBcl-2/Bax ratio modulationCaspase cascade regulationReduced neuronal death[32]
Autophagy regulationmTOR pathway modulationLC3-II, p62 regulationEnhanced cellular waste clearance[33]
Metal ion homeostasisIron/Copper chelationMetal-induced oxidation preventionProtected neural tissue integrity[34]
Synaptic functionBDNF expression enhancementTrkB signaling activationImproved neural plasticity[35]
Protein quality controlHeat shock response activationHSP70, HSP90 inductionEnhanced protein folding capacity[36]
Blood-brain barrierTight junction protectionOccludin/claudin expressionMaintained BBB integrity[37]
Glial supportAstrocyte function modulationGFAP regulationEnhanced neuronal support[38]
Axonal transportMicrotubule stabilizationTau phosphorylation reductionPreserved axonal function[39]
DNA protectionPARP-1 modulationDNA repair enhancementMaintained genomic stability[40]
Calcium homeostasisCa2+ channel regulationIntracellular calcium balanceProtected synaptic transmission[41]
Mitochondrial biogenesisPGC-1α activationEnhanced mitochondrial functionImproved cellular energy status[42]
Neurotransmitter balanceMAO inhibitionDopamine/serotonin regulationEnhanced neurotransmission[43]
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ARE: antioxidant response elements; Aβ: amyloid-beta; BBB: blood-brain barrier; BCL-2: B-cell lymphoma 2; BDNF: brain-derived neurotrophic factor; γ-GCS: gamma-glutamyl cysteine synthetase; GFAP: glial fibrillary acidic protein; HO-1: heme oxygenase 1; HSP: heat shock proteins; IL-1β: interleukin-1β; LC3-II: LC3-phosphatidylethanolamine conjugate; MAO: monoamine oxidase; mTOR: mammalian target of rapamycin; Nrf2: nuclear factor erythroid 2-related factor 2; NQO1: quinone oxidoreductase 1; ONOO−: peroxynitrite; PARP-1: poly (ADP-ribose) polymerase-1; PGC-1α: peroxisome proliferator-activated receptor gamma coactivator 1 alpha; RNS: reactive nitrogen species; ROS: reactive oxygen species; TNF-α: tumor necrosis factor-alpha; TrkB: tropomyosin receptor kinase B