title: Brain-derived and glial cell line-derived neurotrophic factor fusion protein immobilization to laminin.
abstract: Damage to the recurrent laryngeal nerve often causes hoarseness, dyspnea, dysphagia, and sometimes asphyxia due to vocal cord paralysis which result in a reduction of quality of life. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) play critical roles in peripheral nerve regeneration. However, methods for efficiently delivering these molecules are lacking, which limits their use in clinical applications. The present study reports an effective strategy for targeting BDNF and GDNF to laminin by fusing the N-terminal domains of these molecules with agrin (NtA). More specifically, laminin-binding efficacy was assessed and sustained release assays of the delivery of BDNF or GDNF fused with NtA (LBD-BDNF or LBD-GDNF) to laminin were conductedin vitro. In addition, the bioactivity of LBD-BDNF and LBD-GDNF on lamininin vitrowas investigated. LBD-BDNF and LBD-GDNF were each able to specifically bind to laminin and maintain their activityin vitro. Moreover, neurotrophic factors with NtA retained higher concentrations and bioactivity levels compared with those without NtA. The ratio of LBD-BDNF and LBD-GDNF that produced optimal effects was 4:6. BDNF and GDNF fused with NtA were effective in specifically binding to laminin. As laminin is a major component of the extracellular matrix, LBD-BDNF and LBD-GDNF may prove useful in the repair of peripheral nerve injuries.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Shanghai Jiao Tong University Affiliated to Shanghai First People's Hospital, Shanghai 201620, P.R. China.
authors.forename: Baoxin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated to Sixth People's Hospital South Campus, Shanghai 200011, P.R. China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Yuan
authors.affiliation: School of Economics and Finance, Shanghai International Studies University, Shanghai 200083, P.R. China.
authors.forename: Jiafeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Shanghai Jiao Tong University Affiliated to Shanghai First People's Hospital, Shanghai 201620, P.R. China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Shanghai Jiao Tong University Affiliated to Shanghai First People's Hospital, Shanghai 201620, P.R. China.
authors.forename: Xinjiang
authors.initials: X
authors.lastname: Ying
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Shanghai Jiao Tong University Affiliated to Shanghai First People's Hospital, Shanghai 201620, P.R. China.
authors.forename: Pin
authors.initials: P
authors.lastname: Dong
keywords: PC12 cell; brain-derived neurotrophic factor; glial cell line-derived neurotrophic factor; immobilization; laminin