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An l-Glutamine Transporter Isoform for Neurogenesis Facilitated by l-Theanine

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Abstract

l-Theanine (=γ-glutamylethylamide) is an amino acid ingredient in green tea with a structural analogy to l-glutamine (l-GLN) rather than l-glutamic acid (l-GLU), with regards to the absence of a free carboxylic acid moiety from the gamma carbon position. l-theanine markedly inhibits [3H]l-GLN uptake without affecting [3H]l-GLU uptake in cultured neurons and astroglia. In neural progenitor cells with sustained exposure to l-theanine, upregulation of the l-GLN transporter isoform Slc38a1 expression and promotion of both proliferation and neuronal commitment are seen along with marked acceleration of the phosphorylation of mammalian target of rapamycin (mTOR) and relevant downstream proteins. Stable overexpression of Slc38a1 leads to promotion of cellular growth with facilitated neuronal commitment in pluripotent embryonic carcinoma P19 cells. In P19 cells stably overexpressing Slc38a1, marked phosphorylation is seen with mTOR and downstream proteins in a fashion insensitive to the additional stimulation by l-theanine. The green tea amino acid l-theanine could thus elicit pharmacological actions to up-regulate Slc38a1 expression for activation of the mTOR signaling pathway required for cell growth together with accelerated neurogenesis after sustained exposure in undifferentiated neural progenitor cells. In this review, I summarize a novel pharmacological property of the green tea amino acid l-theanine for embryonic and adult neurogenesis with a focus on the endogenous amino acid analog l-GLN. A possible translational strategy is also discussed on the development of dietary supplements and nutraceuticals enriched of l-theanine for the prophylaxis of a variety of untoward impairments and malfunctions seen in patients with different neurodegenerative and/or neuropsychiatric disorders.

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Abbreviations

ADHD:

Attention deficit hyperactivity disorder

AP1:

Activator protein-1

bHLH:

Basic helix-loop-helix

BrdU:

5-bromo-2′-deoxyuridine

CREB:

Cyclic AMP responsive element binding protein

DG:

Dentate gyrus

EAA:

Essential amino acids

ER:

Endoplasmic reticulum

GABA:

γ-aminobutyric acid

GFAP:

Glial fibrillary acidic protein

GFP:

Green fluorescent protein

GLN:

Glutamine

GlnT:

GLN transporter

GLU:

Glutamic acid

MAP2:

Microtubule-associated protein-2

MeAIB:

N-methylaminoisobutyric acid

mTOR:

Mammalian target of rapamycin

MTT:

3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide

NSCs:

Neural stem cells

Slc38a1:

Solute carrier 38a1

XBP1:

X-box binding protein-1

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  1. Section of Prophylactic Pharmacology, Kanazawa University Venture Business Laboratory 402, Kanazawa, Ishikawa, 920–1192, Japan

    Yukio Yoneda

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Yoneda, Y. An l-Glutamine Transporter Isoform for Neurogenesis Facilitated by l-Theanine. Neurochem Res 42, 2686–2697 (2017). https://doi.org/10.1007/s11064-017-2317-6

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