Document Detail


Attenuation of MPTP/MPP(+) Toxicity in vivo and in vitro by an 18-mer Peptide Derived from Prosaposin.
MedLine Citation:
PMID:  23321539     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Parkinson's disease (PD) is a chronic progressive neurological disorder with an increasing incidence in the aging population. Neuroprotective and/or neuroregenerative strategies remain critical in the treatment of this increasingly prevalent disease. Prosaposin is a neurotrophic factor whose neurotrophic activity is attributed to a stretch of 12 amino acids located at the N-terminal region of saposin C. The present study was performed to investigate the protective effect and mechanism of action of a prosaposin-derived 18-mer peptide (PS18: LSELIINNATEELLIKGL) in Parkinson's disease models. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium ion (MPP+)-induced dopaminergic neurotoxicity in C57BL/6J mice or SH-SY5Y cells and explored the protective effect and mechanisms of action of PS18 on dopaminergic neurons. Treatment with 2.0 mg/kg PS18 significantly improved behavioural deficits, enhanced the survival of tyrosine hydroxylase-positive neurons, and decreased the activity of astrocytes in the substantia nigra and striatum in MPTP-induced PD model mice. In vitro, a Cell Counting Kit-8 assay and Hoechst 33258 staining revealed that co-treatment with 300 ng/mL PS18 and 5 mM MPP+ protected against MPP+-induced nuclear morphological changes and attenuated cell death induced by MPP+. We also found that PS18-FAM entered the cells, and the retention time of PS18-FAM in the cytoplasm of MPP+-treated cells was shorter than that of untreated cells. In addition, PS18 showed protection from MPP+/MPTP-induced apoptosis in the SH-SY5Y cells and dopaminergic neurons in the PD model mice via suppression of the c-Jun N-terminal kinase/c-Jun pathway; upregulation of Bcl-2; downregulation of BAX, attenuating mitochondrial damage; and inhibition of caspase-3. These findings suggest that PS18 may provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative diseases such as PD.
Authors:
Hui-Ling Gao; Cheng Li; Hiroaki Nabeka; Tetsuya Shimokawa; Shouichiro Saito; Zhan-You Wang; Ya-Ming Cao; Seiji Matsuda
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-12
Journal Detail:
Title:  Neuroscience     Volume:  -     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013. Published by Elsevier Ltd.
Affiliation:
Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan; College of Life and Health Sciences, Northeastern University, Shenyang, China.
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