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Molecular and Functional Properties of Progranulin

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Progranulin and Central Nervous System Disorders

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Abstract

We have identified progranulin (PGRN) gene as a sex steroid-inducible gene in the brain, which is involved in masculinization of the brain during the perinatal period and facilitation of adult neurogenesis in the hippocampus. PGRN was first reported in early 1990s by different groups as a protein containing seven and a half cysteine-rich granulin domains and having growth promoting properties involved in wound healing and tumorigenesis. Later it was found that mutations of the PGRN gene were associated with neurodegenerative and lysosomal storage diseases such as frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis, respectively. We have also found that PGRN is located in lysosomes and deficiency of PGRN results in exacerbated neuroinflammatory responses and increased lysosomal biogenesis in microglia after traumatic brain injury. It is now recognized that PGRN may regulate activities of lysosomal enzymes as a molecular chaperone and play a crucial role in maintaining cellular protein homeostasis. Deeper understanding of molecular and functional properties of PGRN would provide new insights for developing mechanism-based therapeutic approaches for multiple disorders including cancers and neurodegenerative diseases.

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Authors and Affiliations

  1. Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

    Masugi Nishihara

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  1. Masugi Nishihara
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Correspondence to Masugi Nishihara .

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Editors and Affiliations

  1. Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan

    Hideaki Hara

  2. Dementia Research Project, Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

    Masato Hosokawa

  3. Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan

    Shinsuke Nakamura

  4. Department of Neurology, Gifu University Graduate School of Medicine, Gifu, Japan

    Takayoshi Shimohata

  5. Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

    Masugi Nishihara

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Nishihara, M. (2019). Molecular and Functional Properties of Progranulin. In: Hara, H., Hosokawa, M., Nakamura, S., Shimohata, T., Nishihara, M. (eds) Progranulin and Central Nervous System Disorders. Springer, Singapore. https://doi.org/10.1007/978-981-13-6186-9_1

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