2004 Fiscal Year Final Research Report Summary
Glial Cell Therapy Using Neuroprotective effects of Glia
| Project/Area Number |
15590078
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
TANIGUCHI Takashi Kyoto Pharmaceutical University, Pharmaceutical Sciences, Professor, 薬学部, 教授 (10111957)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Microglia / Astrocytes / Alzheimer's disease / Amyloid-β clearance / Phagocytosis / Rat brain focal ischemia / Cytokines / Neuroprotective effects |
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| Research Abstract |
Recent studies have indicated that prolonged dysfunction and/or stress in the endoplasmic reticulum (ER) may contribute to pathogenesis and neurodegeneration. The disorder caused by misfolding and aggregation of proteins has been referred to as conformational disease, including Alzheimer's disease (AD). AD is characterized by the accumulation of extracellular amyloid-β 1-42 (Aβ42) fibrils with microglia. Understanding the balance of production and clearance of Aβ42 is the key to elucidating amyloid plaque homeostasis. We have recently found that microglial phagocytosis of Aβ42 may be essentially driven by dynamic reorganization of the actin cytoskeleton through the pathway of the Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) and GTP-binding protein Rac1. In addition, an extracellular stress protein, such as heat-shock protein-90 (Hsp90), enhanced Aβ42 phagocytosis. High mobility group box protein-1 (HMGB1) inhibited microglial phagocytosis of Aβ42, and it bound Aβ42 and stabilized the ologomerization. These results suggest that microglial clearance of Aβ42 may be another option for investigations in the search for a therapeutic strategy for AD. Furthermore, although occlusion of the middle cerebral artery (MCA) caused massive neuronal loss, intracerebroventricular-injected microglia migrated into brain damaged parenchyma and then protect against neurodegeneration by focal brain ischemia.
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Research Products
(10 results)
