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P2X7 Receptor Signaling Pathway as a Therapeutic Target for Neurodegenerative Diseases

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

A recent study suggested that neuroinflammation plays a major role in the pathogenesis of a number of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Although the precise mechanism is obscure, dysregulation of the signaling transduction pathway in microglia may enhance inflammation, leading to synaptic dysfunction and ultimately to neuronal cell death. The expression and function of the P2X7 receptor (P2X7R), an ATP-gated ion channel abundantly expressed in microglia in the brain, is significantly up-regulated in the postmortem brain of Alzheimer’s disease patients and various neurodegenerative disease animal models. This supports the role of the P2X7R pathway in the progression of neurodegeneration. Blocking P2X7R using brilliant blue G, a P2X7R antagonist that can cross the blood–brain barrier, has been shown to result in the amelioration of neuropathology in various animal models. Taken together, these results raise the possibility that the P2X7R signaling pathway could be a therapeutic target for treating various neurodegenerative diseases.

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Abbreviations

AD:

Alzheimer’s disease

P2X7R:

P2X7 receptor

Aβ:

Amyloid-β

CNS:

Central nervous system

IL-1β:

Interleukin-1β

PrPSc :

Infectious form of prion protein

HD:

Huntington’s disease

BBG:

Brilliant blue G

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Acknowledgments

This work was supported by a grant-in-aid from the Japanese Ministry of Education, Culture, Sports, Science, and Technology. This work was also supported by a research grant from the Takeda Science Foundation.

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Authors and Affiliations

  1. Laboratory for Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, 183-8526, Japan

    Takato Takenouchi, Kazunari Sekiyama, Akio Sekigawa, Masayo Fujita, Masaaki Waragai, Shuei Sugama & Makoto Hashimoto

  2. Transgenic Animal Research Center, National Institute of Agrobiological Sciences, Ohwashi 1-2, Tsukuba, Ibaraki, 305-8634, Japan

    Takato Takenouchi & Hiroshi Kitani

  3. Prion Disease Research Center, National Institute of Animal Health, Kannondai 3-1-5, Tsukuba, Ibaraki, 305-8602, Japan

    Yoshifumi Iwamaru

Authors
  1. Takato Takenouchi
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  2. Kazunari Sekiyama
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  3. Akio Sekigawa
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  4. Masayo Fujita
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  5. Masaaki Waragai
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  7. Yoshifumi Iwamaru
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  8. Hiroshi Kitani
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  9. Makoto Hashimoto
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Correspondence to Makoto Hashimoto.

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Takenouchi, T., Sekiyama, K., Sekigawa, A. et al. P2X7 Receptor Signaling Pathway as a Therapeutic Target for Neurodegenerative Diseases. Arch. Immunol. Ther. Exp. 58, 91–96 (2010). https://doi.org/10.1007/s00005-010-0069-y

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  • DOI: https://doi.org/10.1007/s00005-010-0069-y

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