作者
Hisatsugu Koshimizu, Kazuyuki Kiyosue, Tomoko Hara, Shunsuke Hazama, Shingo Suzuki, Koichi Uegaki, Guhan Nagappan, Eugene Zaitsev, Takatsugu Hirokawa, Yoshiro Tatsu, Akihiko Ogura, Bai Lu, Masami Kojima
发表日期
2009/12
期刊
Molecular brain
卷号
2
页码范围
1-19
出版商
BioMed Central
简介
Background
Proneurotrophins and mature neurotrophins elicit opposite effects via the p75 neurotrophin receptor (p75NTR) and Trk tyrosine kinase receptors, respectively; however the molecular roles of proneurotrophins in the CNS are not fully understood.
Results
Based on two rare single nucleotide polymorphisms (SNPs) of the human brain-derived neurotrophic factor (BDNF) gene, we generated R125M-, R127L- and R125M/R127L-BDNF, which have amino acid substitution(s) near the cleavage site between the pro- and mature-domain of BDNF. Western blot analyses demonstrated that these BDNF variants are poorly cleaved and result in the predominant secretion of proBDNF. Using these cleavage-resistant proBDNF (CR-proBDNF) variants, the molecular and cellular roles of proBDNF on the CNS neurons were examined. First, CR-proBDNF …
引用总数
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H Koshimizu, K Kiyosue, T Hara, S Hazama, S Suzuki… - Molecular brain, 2009