Novel therapeutic strategy for amyotrophic lateral sclerosis targeting calretinin and monocyte chemoattractant protein-1

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461317
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kyushu University
• Principal Investigator: HAYASHI SHINTARO 九州大学, 医学(系)研究科(研究院), 研究員 (90312876)
• Co-Investigator(Kenkyū-buntansha): OHYAGI YASUMASA 愛媛大学, 医学系研究科, 教授 (30301336) ; TATEISHI TAKAHISA 九州大学, 医学研究院, 共同研究員 (50423546) ; KAWAMURA NOBUTOSHI 九州大学, 医学研究院, 共同研究員 (00432930)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 筋萎縮性側索硬化症 / カルレチニン / 単球走化性蛋白質１ / ミクログリア / マクロファージ / TDP-43 / 脊髄前側索 / カルシウム結合蛋白

Outline of Final Research Achievements

We examined relationships between massive microglia/macrophage (Mi/MΦ) infiltrations in the anterolateral funiculus of amyotrophic lateral sclerosis (ALS) spinal cord and TDP-43 pathology, calretinin (CR, calcium-binding protein), and CCL2 (monocyte chemoattractant protein-1). The results showed that among the Mi/MΦ with various morphologies, the numbers of Mi/MΦ with foamy appearance had a positive correlation with amount of motor neurons with TDP-43 pathology in ALS patients. It was also revealed morphologically that CCL2, elevated in the patient's cerebrospinal fluid, might be derived from the astrocytes. Although, distributions of Mi/MΦ in ALS spinal cord are similar to those of CR-immunoreactive axons in normal human spinal cord, administration of anti-CR antibodies to ALS mouse model (G93A) or CR peptide to normal rat indicated no pathogenicity of CR.

Free Research Field

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