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Energy and Mammalian Target of Rapamycin Complex 1 (mTORC1) in Minimal Change Nephrotic Syndrome

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Molecular Mechanisms in the Pathogenesis of Idiopathic Nephrotic Syndrome

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Abstract

The rupture of the glomerular ultrafiltration barrier due to podocyte injury and loss is considered to be a main pathophysiological cause of glomerular proteinuria in acquired nephrotic syndrome, including minimal change disease. To date, more than 500 protein kinases have been identified, and their functional roles in complicated signaling networks are among the most targeted subjects in the research field of kidney diseases. Currently, signaling network dysregulation is thought to play a crucial role in the pathophysiology involved in so-called podocytopathy, which leads directly to nephrotic syndrome. The proper activation of signaling networks requires sufficient energy within cells. Protein synthesis is tightly regulated and orchestrated by the mammalian target of rapamycin complex 1 (mTORC1) pathway, a major energy-consuming pathway and, by the unfolded protein response (UPR), an energy-economizing pathway. Relatively recent studies have proposed that UPR activation in podocytes is a direct pathophysiological event that causes proteinuria. However, more recent studies, including ours, propose that the excessive activation of mTORC1 acts upstream of UPR, thereby inducing podocyte endoplasmic reticulum stress and leading to nephrotic syndrome.

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Authors and Affiliations

  1. Department of Pediatrics, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan

    Kunimasa Yan

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  1. Kunimasa Yan
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  1. Department of Pediatrics, Kansai Medical University, Hirakata, Osaka, Osaka, Japan

    Kazunari Kaneko

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Yan, K. (2016). Energy and Mammalian Target of Rapamycin Complex 1 (mTORC1) in Minimal Change Nephrotic Syndrome. In: Kaneko, K. (eds) Molecular Mechanisms in the Pathogenesis of Idiopathic Nephrotic Syndrome. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55270-3_5

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  • DOI: https://doi.org/10.1007/978-4-431-55270-3_5

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