Clarification of protective functions of Huntingtin-associated protein 1 against autonomic and motoneuron degeneration using genetically-engineered mice
| Project/Area Number |
20K16108
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 48010:Anatomy-related
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| Research Institution | Yamaguchi University |
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Principal Investigator |
Islam Md Nabiul 山口大学, 大学院医学系研究科, 講師 (80759671)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Stigmoid body / HAP1 / Neuroprotection / Neurodegeneration / STB / Enteric neurons / Autonomic neurons / Enteric nervous system / Motor neuron / Autonomic neuron / Distribution / Immmunohistochemistry |
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| Outline of Research at the Start |
HAP1 can protect neurodegenerative apoptosis in vitro. In this study, to clarify the in vivo effects of HAP1 on protection of autonomic/motoneurons, I will examine the changes of autonomic neurons and their functions using our recently generated HAP1-KO mice by CRISPR-Cas9 mediated genome editing, and differences in motor function behavior test battery between aged-wild-type mice and aged-motor-neuron-specific HAP1-TG mice that we made using Cre-LoxP technology. The outcomes may shed light on yet-to-be-uncovered new diagnostic or therapeutic applications for neurodegenerative diseases.
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| Outline of Final Research Achievements |
Stigmoid body (STB)/Huntingtin-associated protein 1 (HAP1) can bind with the causal agents of several neurodegenerative diseases and suppresses apoptosis and cell death in vitro. STB/HAP1 has been considered a protective factor against neurodegeneration. To uncover a new diagnostic or therapeutic application for autonomic or motor neuron disorders using wild-type and genetically modified mice, in the current research project, I examined the expression, neuroanatomical distribution, and immunohistochemical characterization of STB/HAP1 in the brainstem, sensory ganglia, and enteric ganglion. The results of the current project clarified that STB/HAP1 is highly expressed in the sensory and autonomic neurons in the brainstem, spinal cord, and enteric nervous system but not in motor neurons. These clarify that due to deficient putative STB/HAP1-protection, the motor neurons are more vulnerable to stresses.
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| Academic Significance and Societal Importance of the Research Achievements |
Our current results will lay a basic foundation for future studies that seek to clarify the pathophysiological roles of STB/HAP1 in the motor neuron or autonomic neuron degeneration and may shed light on yet-to-be-uncovered new diagnostic/therapeutic applications of autonomic/ motor neuron diseases.
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Report
(4 results)
Research Products
(42 results)
