The neuroprotective effect of the GSK-3β inhibitor and influence on the extrinsic apoptosis in the ALS transgenic mice

Suk Won Ahn, Jee Eun Kim, Kyung Seok Park, Won Jun Choi, Yoon Ho Hong, Sung Min Kim, Seung Hyun Kim, Kwang Woo Lee, Jung Joon Sung

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Background: Glycogen synthase kinase-3β (GSK-3β) activity plays a central role in motor neuron degeneration. We hypothesized that GSK-3β inhibitor would prolong the survival of motor neuron and suppress the disease progression in amyotrophic lateral sclerosis (ALS). Methods: A total of 40 transgenic mice harboring the human G93A mutated SOD1 gene and 14 wild type mice were used following confirmation of their genotype. The 40 transgenic mice were divided into 2 groups; ALS transgenic mice-control and ALS transgenic mice-GSK-3β inhibitor treatment. The clinical status, rotarod test and survival of the transgenic ALS mice and wild-type mice were evaluated. Additionally, motor neuron counting, GSK-3β activity and extrinsic apoptotic signals in spinal cord were also investigated. Results: The treatment with GSK-3β inhibitor showed excellent motor ability and delay of the symptom onset and survival in the ALS transgenic mice. However, after clinical symptoms developed, the neuroprotective effect of GSK-3β inhibitor was not significant. And the biochemical results revealed the weakly increased extrinsic apoptotic signals in the ALS transgenic mice by GSK-3β inhibitor treatment. Conclusion: The present study suggests that GSK-3β inhibitor would be a novel promising therapeutic strategy in ALS; however neuroprotective effect of GSK-3β inhibitor may be reduced via extrinsic apoptosis or non-neuronal patho-mechanism in late-stage of disease.

Original languageEnglish
Pages (from-to)1-5
Number of pages5
JournalJournal of the Neurological Sciences
Issue number1-2
StatePublished - 15 Sep 2012

Bibliographical note

Funding Information:
This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea ( A091049 ).


  • ALS
  • Amyotrophic lateral sclerosis
  • Extrinsic apoptosis
  • GSK-3β inhibitor
  • Glycogen synthase kinase-3


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