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.
Export Options
About this article
Cite this article as:
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 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Pharmacological Targets for the Inhibition of Neurogenic Inflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Polyethylenimine as a Promising Vector for Targeted siRNA Delivery
Current Clinical Pharmacology Therapeutic Application of Histone Deacetylase Inhibitors for Stroke
Central Nervous System Agents in Medicinal Chemistry Therapeutic Drug Monitoring of Busulfan in Transplantation
Current Pharmaceutical Design The Renin Angiotensin System in the Regulation of Angiogenesis
Current Pharmaceutical Design Treatment of Alzheimer's Disease: Classical Therapeutic Approach
Current Pharmaceutical Analysis Kinetic Study on the Effects of Extremely Low Frequency Electromagnetic Field on Catalase, Cytochrome P450 and Inducible Nitric Oxide Synthase in Human HaCaT and THP-1 Cell Lines
CNS & Neurological Disorders - Drug Targets Neuroprotection by Resveratrol in Diabetic Neuropathy: Concepts & Mechanisms
Current Medicinal Chemistry Platelet-Activating Factor (PAF) Antagonists Attenuate Inflammatory- Based Pain: Potential Cellular and Anatomical Sites of PAF Action
Central Nervous System Agents in Medicinal Chemistry Implication of Possible Therapies Targeted for the Tachykinergic System with the Biology of Neurokinin Receptors and Emerging Related Proteins
Recent Patents on CNS Drug Discovery (Discontinued) Natural Compounds as Antagonists of Canonical Wnt/β-Catenin Signaling
Current Chemical Biology Angiogenesis Inhibition in the Treatment of Prostate Cancer
Anti-Cancer Agents in Medicinal Chemistry HtrA Protease Family as Therapeutic Targets
Current Pharmaceutical Design Establishing Genomic/Transcriptomic Links Between Alzheimer’s Disease and Type 2 Diabetes Mellitus by Meta-Analysis Approach
CNS & Neurological Disorders - Drug Targets Mechanisms Involved in BACE Upregulation Associated to Stress
Current Alzheimer Research Development of a Novel and Robust Pharmacological Model of Okadaic Acid-induced Alzheimer’s Disease in Zebrafish
CNS & Neurological Disorders - Drug Targets ABC Transporters in the Development of Multidrug Resistance in Cancer Therapy
Current Pharmaceutical Design MicroRNAs: Emerging Role in the Endogenous μ Opioid System
CNS & Neurological Disorders - Drug Targets PLK1 Inhibition: Prospective Role for the Treatment of Pediatric Tumors
Current Drug Targets Endoplasmic Reticulum Stress as a Novel Therapeutic Target in Heart Diseases
Cardiovascular & Hematological Disorders-Drug Targets