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The interactions of flavonoids within neuronal signalling pathways

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Abstract

Emerging evidence suggests that dietary phytochemicals, in particular flavonoids, may exert beneficial effects in the central nervous system by protecting neurons against stress-induced injury, by suppressing neuroinflammation and by promoting neurocognitive performance, through changes in synaptic plasticity. It is likely that flavonoids exert such effects in neurons, through selective actions on different components within a number of protein kinase and lipid kinase signalling cascades, such as phosphatidylinositol-3 kinase (PI3K)/Akt, protein kinase C and mitogen-activated protein kinase. This review details the potential inhibitory or stimulatory actions of flavonoids within these pathways, and describes how such interactions are likely to affect cellular function through changes in the activation state of target molecules and/or by modulating gene expression. Although, precise sites of action are presently unknown, their abilities to: (1) bind to ATP binding sites on enzymes and receptors; (2) modulate the activity of kinases directly; (3) affect the function of important phosphatases; (4) preserve neuronal Ca2+ homeostasis; and (5) modulate signalling cascades lying downstream of kinases, are explored. Future research directions are outlined in relation to their precise site(s) of action within the signalling pathways and the sequence of events that allow them to regulate neuronal function in the central nervous system.

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Abbreviations

MAPK:

Mitogen-activated protein kinase

ERK:

Extracellular signal-regulated protein kinase

JNK:

c-Jun N-terminal kinase

PI3K:

Phosphatidylinositol-3 kinase

PKB:

Protein kinase B

PKC:

Protein kinase C

ASK1:

Apoptosis signal-regulating kinase 1

STAT-1:

Signal transducer and activator of transcription-1

AP-1:

Activated protein-1

CREB:

cAMP response element-binding protein

ATF-1/2:

Activating transcription factor 1/2

MSK1:

Mitogen- and stress-activated protein kinase 1

MTOR:

Mammalian target of rapamycin

p47phox :

NADPH oxidase (p47 cytoplasmic element; p90RSK (RSK): 90 kDa ribosomal S6 kinase

MEF-2:

Myocyte enhancer factor 2

DSP:

Dual specificity phosphatase

PTEN:

Phosphatase and tensin homologue deleted on chromosome ten

LPS:

Lipopolysacharide

IL-1β:

Interleukin-1β

INOS:

Inducible nitric oxide synthase

ENOS:

Endothelial nitric oxide synthase

IFN-γ:

Interferon gamma

LDL:

Low-density lipoprotein

NO• :

Nitric oxide

TNF-α:

Tumor necrosis factor-alpha

BBB:

Blood brain barrier

CNS:

Central nervous system

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Acknowledgments

Dr. Jeremy Spencer is sponsored by the Biotechnology and Biological Sciences Research Council (BB/C518222/1) and the Medical Research Council (G0400278/NI02).

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    Jeremy P. E. Spencer

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Spencer, J.P.E. The interactions of flavonoids within neuronal signalling pathways. Genes Nutr 2, 257–273 (2007). https://doi.org/10.1007/s12263-007-0056-z

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