Abstract
Prosaposin, a 66 kDa glycoprotein, was identified initially as the precursor of the sphingolipid activator proteins, saposins A-D, which are required for the enzymatic hydrolysis of certain sphingolipids by lysosomal hydrolases. While mature saposins are distributed to lysosomes, prosaposin exists in secretory body fluids and plasma membranes. In addition to its role as the precursor, prosaposin shows a variety of neurotrophic and myelinotrophic activities through a receptor- mediated mechanism. In studies in vivo, prosaposin was demonstrated to exert a variety of neuro-efficacies capable of preventing neuro-degeneration following neuro-injury and promoting the amelioration of allodynia and hyperalgesia in pain models. Collective findings indicate that prosaposin is not a simple house-keeping precursor protein; instead, it is a protein essentially required for the development and maintenance of the central and peripheral nervous systems. Accumulating evidence over the last decade has attracted interests in exploring and developing new therapeutic approaches using prosaposin for human disorders associated with neuro-degeneration. In this review we detail the structure characteristics, cell biological feature, in vivo efficacy, and neuro-therapeutic potential of prosaposin, thereby providing future prospective in clinical application of this multifunctional protein.
Central Nervous System Agents in Medicinal Chemistry
Title: Biochemistry and Neurobiology of Prosaposin: A Potential Therapeutic Neuro-Effector
Volume: 9 Issue: 2
Author(s): Roberta Misasi, Isao Hozumi, Takashi Inuzuka, Antonella Capozzi, Vincenzo Mattei, Yukako Kuramoto, Hiroshi Shimeno, Shinji Soeda, Norihiro Azuma, Toyoaki Yamauchi and Masao Hiraiwa
Affiliation:
Abstract: Prosaposin, a 66 kDa glycoprotein, was identified initially as the precursor of the sphingolipid activator proteins, saposins A-D, which are required for the enzymatic hydrolysis of certain sphingolipids by lysosomal hydrolases. While mature saposins are distributed to lysosomes, prosaposin exists in secretory body fluids and plasma membranes. In addition to its role as the precursor, prosaposin shows a variety of neurotrophic and myelinotrophic activities through a receptor- mediated mechanism. In studies in vivo, prosaposin was demonstrated to exert a variety of neuro-efficacies capable of preventing neuro-degeneration following neuro-injury and promoting the amelioration of allodynia and hyperalgesia in pain models. Collective findings indicate that prosaposin is not a simple house-keeping precursor protein; instead, it is a protein essentially required for the development and maintenance of the central and peripheral nervous systems. Accumulating evidence over the last decade has attracted interests in exploring and developing new therapeutic approaches using prosaposin for human disorders associated with neuro-degeneration. In this review we detail the structure characteristics, cell biological feature, in vivo efficacy, and neuro-therapeutic potential of prosaposin, thereby providing future prospective in clinical application of this multifunctional protein.
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Misasi Roberta, Hozumi Isao, Inuzuka Takashi, Capozzi Antonella, Mattei Vincenzo, Kuramoto Yukako, Shimeno Hiroshi, Soeda Shinji, Azuma Norihiro, Yamauchi Toyoaki and Hiraiwa Masao, Biochemistry and Neurobiology of Prosaposin: A Potential Therapeutic Neuro-Effector, Central Nervous System Agents in Medicinal Chemistry 2009; 9 (2) . https://dx.doi.org/10.2174/187152409788452045
DOI https://dx.doi.org/10.2174/187152409788452045 |
Print ISSN 1871-5249 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6166 |
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