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Targeting Necroptosis as Therapeutic Potential in Central Nervous System Diseases

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Handbook of Neurotoxicity

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Abstract

Necroptosis is a regulated cell death (RCD) induced by receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL). Studies have shown that necroptosis plays an important role in many diseases, including central nervous system diseases and peripheral system diseases. The main molecular mechanisms which govern necroptosis, upstream and downstream signaling pathways, and related molecular inhibitors were discussed in this chapter. Furthermore, ample evidence shows that necroptosis is involved in the process of neurological diseases. With in-depth research on the molecular mechanism of necroptosis, this chapter will provide new insights to develop neuroprotectants against it and specific therapeutic strategies for clinical treatment of neurological disorders.

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Abbreviations

ACD:

Accidental cell death

AD:

Alzheimer’s disease

AIF:

Apoptosis inducing factor

ALS:

Amyotrophic lateral sclerosis

BBB:

Blood-brain barrier

DD:

Death domain

DRs:

Death receptors

HIE:

Hypoxic-ischemic encephalopathy

ICH:

Intracerebral hemorrhage

MCAO:

Middle cerebral artery occlusion

MLKL:

Mixed lineage kinase domain-like protein

PCD:

Programmed cell death

RCD:

Regulated cell death

RIPK3:

Receptor interacting protein kinase 3

SAH:

Subarachnoid hemorrhage

TRADD:

TNF-receptor-associated death domain

TRAF:

TNF-receptor-associated factor

TRAIL:

TNF-related apoptosis inducing ligand

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Author notes

  1. Hao Li and Meiling Xia contributed equally with all other contributors.

Authors and Affiliations

  1. Departments of Neurology, The First Affiliated Hospital of Soochow University, Suzhou City, China

    Hao Li & Xingshun Xu

  2. Departments of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou City, China

    Meiling Xia & Jing Chen

  3. Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA

    Richard Kostrzewa

  4. Institute of Neuroscience, Soochow University, Suzhou City, China

    Xingshun Xu

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  1. Hao Li
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  2. Meiling Xia
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  3. Jing Chen
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  4. Richard Kostrzewa
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  5. Xingshun Xu
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Corresponding author

Correspondence to Xingshun Xu .

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Editors and Affiliations

  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

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Li, H., Xia, M., Chen, J., Kostrzewa, R., Xu, X. (2021). Targeting Necroptosis as Therapeutic Potential in Central Nervous System Diseases. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-030-71519-9_166-1

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  • DOI: https://doi.org/10.1007/978-3-030-71519-9_166-1

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  • Print ISBN: 978-3-030-71519-9

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