Protein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Neurosci Res. 2010 Sep;68(1):35-43. doi: 10.1016/j.neures.2010.05.002. Epub 2010 May 16.
Hexafins are recently identified low-molecular-weight peptide agonists of the fibroblast growth factor receptor (FGFR), derived from the beta6-beta7 loop region of various FGFs. Synthetic hexafin peptides have been shown to bind to and induce tyrosine phosphorylation of FGFR1, stimulate neurite outgrowth, and promote neuronal survival in vitro. Thus, the pronounced biological activities of hexafins in vitro make them attractive compounds for pharmacological studies in vivo. The present study investigated the effects of subcutaneous administration of hexafin1 and hexafin2 (peptides derived from FGF1 and FGF2, respectively) on social memory, exploratory activity, and anxiety-like behavior in adult rats. Treatment with hexafin1 and hexafin2 resulted in prolonged retention of social memory. Furthermore, rats treated with hexafin2 exhibited decreased anxiety-like behavior in the elevated plus maze. Employing an R6/2 mouse model of Huntington's disease (HD), we found that although hexafin2 did not affect the progression of motor symptoms, it alleviated deficits in activity related to social behavior, including sociability and social novelty. Thus, hexafin2 may have therapeutic potential for the treatment of HD.
六肽是最近发现的成纤维细胞生长因子受体（FGFR）的低分子量肽激动剂，来源于各种 FGF 的β6-β7 环区。合成的六肽已被证明可以结合并诱导 FGFR1 的酪氨酸磷酸化，刺激神经突生长，并在体外促进神经元存活。因此，六肽在体外表现出的显著生物学活性使它们成为体内药理学研究有吸引力的化合物。本研究探讨了皮下给予六肽 1 和六肽 2（分别来源于 FGF1 和 FGF2 的肽）对成年大鼠社交记忆、探索活动和焦虑样行为的影响。用六肽 1 和六肽 2 处理可延长社交记忆的保留时间。此外，用六肽 2 处理的大鼠在高架十字迷宫中表现出焦虑样行为减少。在亨廷顿病（HD）的 R6/2 小鼠模型中，我们发现尽管六肽 2 不影响运动症状的进展，但它减轻了与社交行为相关的活动缺陷，包括社交性和社交新颖性。因此，六肽 2 可能具有治疗 HD 的潜力。
