SARM1 is responsible for calpain-dependent dendrite degeneration in mouse hippocampal neurons
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作者:
Miyamoto, Takashi
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Denali Therapeut Inc, South San Francisco, CA 94080 USADenali Therapeut Inc, South San Francisco, CA 94080 USA
Miyamoto, Takashi
[1
]
Kim, Chaeyoung
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Denali Therapeut Inc, South San Francisco, CA 94080 USADenali Therapeut Inc, South San Francisco, CA 94080 USA
Kim, Chaeyoung
[1
]
Chow, Johann
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Denali Therapeut Inc, South San Francisco, CA 94080 USADenali Therapeut Inc, South San Francisco, CA 94080 USA
Chow, Johann
[1
]
Dugas, Jason C.
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Denali Therapeut Inc, South San Francisco, CA 94080 USADenali Therapeut Inc, South San Francisco, CA 94080 USA
Dugas, Jason C.
[1
]
Degroot, Jack
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Denali Therapeut Inc, South San Francisco, CA 94080 USA
Intellia Therapeut Inc, 40 Erie St, Cambridge, MA 02139 USADenali Therapeut Inc, South San Francisco, CA 94080 USA
Degroot, Jack
[1
,2
]
Bagdasarian, Alex L.
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Denali Therapeut Inc, South San Francisco, CA 94080 USADenali Therapeut Inc, South San Francisco, CA 94080 USA
Bagdasarian, Alex L.
[1
]
Thottumkara, Arun P.
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Denali Therapeut Inc, South San Francisco, CA 94080 USA
Odyssey Therapeut, 4242 Campus Point Ct, San Diego, CA 92121 USADenali Therapeut Inc, South San Francisco, CA 94080 USA
Thottumkara, Arun P.
[1
,3
]
Larhammar, Martin
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Denali Therapeut Inc, South San Francisco, CA 94080 USA
BioArct, Warfvinges Vag 35, S-11251 Stockholm, SwedenDenali Therapeut Inc, South San Francisco, CA 94080 USA
Larhammar, Martin
[1
,4
]
Calvert, Meredith E. K.
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Denali Therapeut Inc, South San Francisco, CA 94080 USADenali Therapeut Inc, South San Francisco, CA 94080 USA
Calvert, Meredith E. K.
[1
]
Fox, Brian M.
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Denali Therapeut Inc, South San Francisco, CA 94080 USADenali Therapeut Inc, South San Francisco, CA 94080 USA
Fox, Brian M.
[1
]
Lewcock, Joseph W.
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Denali Therapeut Inc, South San Francisco, CA 94080 USADenali Therapeut Inc, South San Francisco, CA 94080 USA
Lewcock, Joseph W.
[1
]
Kane, Lesley A.
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Denali Therapeut Inc, South San Francisco, CA 94080 USADenali Therapeut Inc, South San Francisco, CA 94080 USA
Kane, Lesley A.
[1
]
机构:
[1] Denali Therapeut Inc, South San Francisco, CA 94080 USA
[2] Intellia Therapeut Inc, 40 Erie St, Cambridge, MA 02139 USA
[3] Odyssey Therapeut, 4242 Campus Point Ct, San Diego, CA 92121 USA
[4] BioArct, Warfvinges Vag 35, S-11251 Stockholm, Sweden
Sterile alpha and toll/interleukin receptor motif-containing 1 (SARM1) is a critical regulator of axon degeneration that acts through hydrolysis of NAD+ following injury. Recent work has defined the mechanisms underlying SARM1's catalytic activity and advanced our understanding of SARM1 function in axons, yet the role of SARM1 signaling in other compartments of neurons is still not well understood. Here, we show in cultured hippocampal neurons that endogenous SARM1 is present in axons, dendrites, and cell bodies and that direct activation of SARM1 by the neurotoxin Vacor causes not just axon degeneration, but degeneration of all neuronal compartments. In contrast to the axon degeneration pathway defined in dorsal tion in vitro is not sensitive to inhibition of calpain proteases. Dendrite degeneration downstream of SARM1 in hippocampal neurons is dependent on calpain 2, a calpain protease isotype enriched in dendrites in this cell type. In summary, these data indicate SARM1 plays a critical role in neurodegeneration outside of axons and elucidates divergent pathways leading to degeneration in hippocampal axons and dendrites.
机构:
Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
Univ Chinese Acad Sci, Beijing 100049, Peoples R ChinaChinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
Yue, Wenkai
Zhang, Kai
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Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
Univ Chinese Acad Sci, Beijing 100049, Peoples R ChinaChinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
Zhang, Kai
Jiang, Mingsheng
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机构:
Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
Univ Chinese Acad Sci, Beijing 100049, Peoples R ChinaChinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
Jiang, Mingsheng
Long, Wenjing
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机构:
Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
Univ Chinese Acad Sci, Beijing 100049, Peoples R ChinaChinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
Long, Wenjing
Cui, Jihong
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Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R ChinaChinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
Cui, Jihong
Li, Yunxia
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Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R ChinaChinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
Li, Yunxia
Zhang, Yaoyang
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Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
Univ Chinese Acad Sci, Beijing 100049, Peoples R ChinaChinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
Zhang, Yaoyang
Li, Ang
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机构:
Jinan Univ, GHM Inst CNS Regenerat, Guangdong Key Lab Nonhuman Primate Res, Key Lab CNS Regenerat,Minist Educ, Guangzhou 510632, Peoples R ChinaChinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
Li, Ang
Fang, Yanshan
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Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
Univ Chinese Acad Sci, Beijing 100049, Peoples R ChinaChinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China
机构:
Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA
Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USAUniv Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA
机构:
Washington Univ, Needleman Ctr Neurometab & Axonal Therapeut, Sch Med, St Louis, MO 63110 USA
Washington Univ, Genome Engn & iPSC Ctr, Sch Med, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA
Chen, Yi-Hsien
Sasaki, Yo
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Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA
Sasaki, Yo
DiAntonio, Aaron
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机构:
Washington Univ, Dept Dev Biol, Sch Med, St Louis, MO 63110 USA
Washington Univ, Needleman Ctr Neurometab & Axonal Therapeut, Sch Med, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA
DiAntonio, Aaron
Milbrandt, Jeffrey
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机构:
Washington Univ, Dept Dev Biol, Sch Med, St Louis, MO 63110 USA
Washington Univ, Needleman Ctr Neurometab & Axonal Therapeut, Sch Med, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA