Presence of proNGF-sortilin signaling complex in nigral dopamine neurons and its Variation in relation to aging, lactacystin and 6-OHDA insults

Yi Xia, Bei Yu Chen, Xiao Long Sun, Li Duan, Guo Dong Gao, Jing Jie Wang*, Kin Lam YUNG, Liang Wei Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Growing evidence has shown that proNGF-p75NTR-sortilin signaling might be a crucial factor in neurodegeneration, but it remains unclear if it may function in nigral neurons under aging and disease. The purpose of this study is to examine and quantify proNGF and sortilin expression in the substantia nigra and dynamic changes of aging in lactacystin and 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease using immunofluorescence, electronic microscopy, western blot and FLIVO staining methods. The expression of proNGF and sortilin was abundantly and selectively identified in tyrosine hydroxylase (TH)-containing dopamine neurons in the substantia nigra. These proNGF/TH, sortilin/TH-positive neurons were densely distributed in the ventral tier, while they were less distributed in the dorsal tier, where calbindin-D28K-containing neurons were numerously located. A correlated decrease of proNGF, sortilin and TH was also detected during animal aging process. While increase of proNGF, sortilin and cleaved (active) caspase-3 expression was found in the lactacystin model, dynamic proNGF and sortilin changes along with dopamine neuronal loss were demonstrated in the substantia nigra of both the lactacystin and 6-OHDA models. This study has thus revealed the presence of the proNGF-sortilin signaling complex in nigral dopamine neurons and its response to aging, lactacystin and 6-OHDA insults, suggesting that it might contribute to neuronal apoptosis or neurodegeneration during pathogenesis and disease progression of Parkinson's disease; the underlying mechanism and key signaling pathways involved warrant further investigation.

Original languageEnglish
Pages (from-to)14085-14104
Number of pages20
JournalInternational Journal of Molecular Sciences
Volume14
Issue number7
DOIs
Publication statusPublished - Jul 2013

Scopus Subject Areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

User-Defined Keywords

  • Neurodegeneration
  • Parkinson's disease
  • Pro-neurotrophin receptors
  • Pro-neurotrophins

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