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HMGB1 in Development and Diseases of the Central Nervous System

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Abstract

High mobility group box 1 (HMGB1) is widely expressed in cells of vertebrates in two forms: a nuclear “architectural” factor and a secreted inflammatory factor. During early brain development, HMGB1 displays a complex temporal and spatial distribution pattern in the central nervous system. It facilitates neurite outgrowth and cell migration critical for processes, such as forebrain development. During adulthood, HMGB1 serves to induce neuroinflammation after injury, such as lesions in the spinal cord and brain. Receptor for advanced glycation end products and Toll-like receptors signal transduction pathways mediate HMGB1-induced neuroinflammation and necrosis. Increased levels of endogenous HMGB1 have also been detected in neurodegenerative diseases. However, in Huntington’s disease, HMGB1 has been reported to protect neurons through activation of apurinic/apyrimidinic endonuclease and 5′-flap endonuclease-1, whereas in other neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, HMGB1 serves as a risk factor for memory impairment, chronic neurodegeneration, and progression of neuroinflammation. Thus, HMGB1 plays important and double-edged roles during neural development and neurodegeneration. The HMGB1-mediated pathological mechanisms have remained largely elusive. Knowledge of these mechanisms is likely to lead to therapeutic targets for neurological diseases.

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Acknowledgments

We sincerely thank Dr. Stanley Li Lin for his helpful discussion and critical language editing of the manuscript. We are also grateful to Drs. Heikki Rauvala, Firoze Jungalwala, and AnnMarie Schmidt for their thoughtful comments. This project is supported by NNSF, China (81072622) and the Li Kashing Foundation. We hope that we cited all publications relevant for this review and apologize to those groups if their publications are not adequately cited due to the limited search tools at our disposal.

Conflict of Interest

The authors declare that there are no conflict interests.

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  1. Center for Neuroscience, Shantou University Medical College, Shantou, 515041, China

    Ping Fang, Melitta Schachner & Yan-Qin Shen

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Correspondence to Melitta Schachner or Yan-Qin Shen.

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Fang, P., Schachner, M. & Shen, YQ. HMGB1 in Development and Diseases of the Central Nervous System. Mol Neurobiol 45, 499–506 (2012). https://doi.org/10.1007/s12035-012-8264-y

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