Neuroprotective effect of NXP031 in the MPTP-induced Parkinson's disease model

TY - JOUR

T1 - Neuroprotective effect of NXP031 in the MPTP-induced Parkinson's disease model

AU - Song, Min Kyung

AU - Lee, Joo Hee

AU - Kim, Jinil

AU - Kim, Ji Hyun

AU - Hwang, Soonhye

AU - Kim, Yoon Seong

AU - Kim, Youn Jung

N1 - Funding Information: This work was supported by Nexmos (2 0182507U0054101S000100 ) and N ational Research Foundation of Korea (NRF) funded by the M inistry of Education, Science, and Technology ( N RF-2020R1A2B5B0100276611 ) Funding Information: This work was supported by Nexmos (<GN1>2</GN1>0182507U0054101S000100) and National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (NRF-2020R1A2B5B0100276611) Publisher Copyright: © 2020

PY - 2021/1/1

Y1 - 2021/1/1

N2 - Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN). Oxidative stress has been identified as one of the major causes of nigrostriatal degeneration in PD. Ascorbic acid plays a role as an efficient antioxidant to protect cells from free radical damage, but it is easily oxidized and loses its antioxidant activity. To overcome this limitation, we have recently developed NXP031, a single-stranded DNA aptamer that binds to ascorbic acid with excellent specificity, reducing its oxidation and increasing its efficacy. This study investigated the neuroprotective effects of NXP031 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model. Acute degeneration of nigral dopaminergic neurons was induced by four consecutive treatments of MPTP (20 mg/kg) in male C57BL/6 J mice. NXP031 (Vitamin C/Aptamin C 200 mg/4 mg/kg) was administered intraperitoneally for 5 days following MPTP. We observed that the administration of NXP031 ameliorated MPTP-induced loss of dopaminergic neurons in the SN and exhibited improvement of MPTP-mediated motor impairment. We further found that NXP031 increased plasma ascorbic acid levels and inhibited microglia activation-induced neuroinflammation in the SN, which might contribute to the protective effects of NXP031 on nigrostriatal degeneration. Our findings suggest that NXP031 could be a potential therapeutic intervention in PD.

AB - Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN). Oxidative stress has been identified as one of the major causes of nigrostriatal degeneration in PD. Ascorbic acid plays a role as an efficient antioxidant to protect cells from free radical damage, but it is easily oxidized and loses its antioxidant activity. To overcome this limitation, we have recently developed NXP031, a single-stranded DNA aptamer that binds to ascorbic acid with excellent specificity, reducing its oxidation and increasing its efficacy. This study investigated the neuroprotective effects of NXP031 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model. Acute degeneration of nigral dopaminergic neurons was induced by four consecutive treatments of MPTP (20 mg/kg) in male C57BL/6 J mice. NXP031 (Vitamin C/Aptamin C 200 mg/4 mg/kg) was administered intraperitoneally for 5 days following MPTP. We observed that the administration of NXP031 ameliorated MPTP-induced loss of dopaminergic neurons in the SN and exhibited improvement of MPTP-mediated motor impairment. We further found that NXP031 increased plasma ascorbic acid levels and inhibited microglia activation-induced neuroinflammation in the SN, which might contribute to the protective effects of NXP031 on nigrostriatal degeneration. Our findings suggest that NXP031 could be a potential therapeutic intervention in PD.

KW - Aptamer

KW - MPTP

KW - NXP031

KW - Neuroprotection

KW - Parkinson's disease

KW - Vitamin C

UR - http://www.scopus.com/inward/record.url?scp=85093669352&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85093669352&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.neulet.2020.135425

DO - https://doi.org/10.1016/j.neulet.2020.135425

M3 - Article

C2 - 33075422

SN - 0304-3940

VL - 740

JO - Neuroscience Letters

JF - Neuroscience Letters

M1 - 135425

ER -