Neural Regeneration Research ›› 2013, Vol. 8 ›› Issue (35): 3269-3274.doi: 10.3969/j.issn.1673-5374.2013.35.001

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Nanomolar concentration of alpha-synuclein enhances dopaminergic neuronal survival via Akt pathway

Ji-Young Kim1, Beom Seok Jeon2, Han-Joon Kim2, Tae-Beom Ahn3   

  1. 1 Department of Neurology, Inje University Seoul Paik Hospital, Seoul, South Korea
    2 Department of Neurology, College of Medicine, Seoul National University Hospital, Seoul, South Korea
    3 Department of Neurology, Kyung Hee University Medical Center, Seoul, South Korea
  • Received:2013-08-14 Revised:2013-11-18 Online:2013-12-15 Published:2013-12-15
  • Contact: Beom S. Jeon, M.D., Ph.D., Professor, Department of Neurology, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-744, South Korea, brain@snu.ac.kr.
  • About author:Ji-Young Kim, M.D.
  • Supported by:

    This work was supported by the Seoul National University Hospital (SNUH) Research Fund, No. 03-2010-0240.

Abstract:

Although alpha-synuclein is generally thought to have a pathological role in Parkinson’s disease, accumulative evidence exists that alpha-synuclein has a neuroprotective effect. The aim of this study was to evaluate the effect of extracellular alpha-synuclein on dopaminergic cell survival. We assessed cell viability using the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltertazolium bromide (MTT) assay both in undifferentiated SH-SY5Y (SHSY) cells and neuronally-differentiated SH-SY5Y (ndSHSY) cells after 24 hour treatment with monomeric alpha-synuclein at various concentrations (0 [control], 50, 100 nmol/L, 1 μmol/L). To determine whether cell viability assessed by MTT assay was affected by cell proliferation, 5-bromo-2'-deoxyuridine (BrdU) incorporation assay was per-formed. Level of both Akt and phosphorylated Akt was measured using western blot method in ndSHSY cells with or without 24 hour alpha-synuclein treatment. Cell viability was increased in ndSHSY cells at the nanomolar concentration of alpha-synuclein, but not in SHSY cells. Proportion of BrdU-positive ndSHSY cells was decreased in alpha-synuclein-treated group compared with control group. Level of phosphorylated Akt in alpha-synuclein-treated group was higher compared with the control group. Our study shows that extracellular alpha-synuclein at nanomolar concentra-tion benefits dopaminergic cell survival via Akt pathway.

Key words: neural regeneration, alpha-synuclein, neuronal survival, nanomolar, extracellular, phosphorylated Akt, SH-SY5Y cell, neuronal differentiation, proliferation, dopaminergic, 5-bromo-2'-deoxyuridine, grants-supported paper, neuroregeneration