The Protective Effects of Levetiracetam on a Human iPSCs-Derived Spinal Muscular Atrophy Model

被引：17

作者：

Ando, Shiori ^{[1
,2
]}

Funato, Michinori ^{[2
]}

Ohuchi, Kazuki ^{[1
,2
]}

Inagaki, Satoshi ^{[1
,2
]}

Sato, Arisu ^{[1
,2
]}

Seki, Junko ^{[2
]}

Kawase, Chizuru ^{[2
]}

Saito, Toshio ^{[3
]}

Nishio, Hisahide ^{[4
]}

Nakamura, Shinsuke ^{[1
]}

Shimazawa, Masamitsu ^{[1
]}

Kaneko, Hideo ^{[2
]}

Hara, Hideaki ^{[1
]}

机构：

[1] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan

[2] Natl Hosp Org, Nagara Med Ctr, Dept Clin Res, Gifu, Japan

[3] Natl Hosp Org, Toneyama Natl Hosp, Dept Neurol, Div Child Neurol, Toyonaka, Osaka, Japan

[4] Kobe Gakuin Univ, Fac Rehabil, Dept Occupat Therapy, Kobe, Hyogo, Japan

来源：

NEUROCHEMICAL RESEARCH | 2019年 / 44卷 / 07期

关键词：

Spinal muscular atrophy; Induced pluripotent stem cells; Levetiracetam; Motor neuron; PLURIPOTENT STEM-CELLS; MITOCHONDRIAL DYSFUNCTION; OPEN-LABEL; PROTEIN; APOPTOSIS; GENE; CALCIUM; BINDING;

D O I：

10.1007/s11064-019-02814-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Spinal muscular atrophy (SMA) is an inherited disease characterized by progressive motor neuron death and subsequent muscle weakness and is caused by deletion or mutation of survival motor neuron (SMN) 1 gene. Protecting spinal motor neuron is an effective clinical strategy for SMA. The purpose of this study was to investigate the potential effect of an anti-epileptic drug levetiracetam on SMA. In the present study, we used differentiated spinal motor neurons (MNs) from SMA patient-derived induced pluripotent stem cells (SMA-iPSCs) to investigate the effect of levetiracetam. Levetiracetam promoted neurite elongation in SMA-iPSCs-MNs. TUNEL-positive spinal motor neurons were significantly reduced by levetiracetam in SMA-iPSCs-MNs. In addition, the expression level of cleaved-caspase 3 was decreased by levetiracetam in SMA-iPSCs-MNs. Furthermore, levetiracetam improved impaired mitochondrial function in SMA-iPSCs-MNs. On the other hand, levetiracetam did not affect the expression level of SMN protein in SMA-iPSCs-MNs. These findings indicate that levetiracetam has a neuroprotective effect for SMA.

引用

页码：1773 / 1779

页数：7

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