Weiss Joseph B, Weber Sydney, Marzulla Tessa, Raber Jacob
Cardiovascular Institute and Warren Alpert School of Medicine at Brown University Providence, RI 02840, USA.
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
Behav Brain Res. 2017 Aug 14;332:337-342. doi: 10.1016/j.bbr.2017.06.024. Epub 2017 Jun 16.
Heterozygous Neurofibromatosis 1 (NF1) loss of function mutations are found in 90% of patients with neurofibromatosis, a syndrome associated with disabling cognitive impairment. Drosophila studies have demonstrated a genetic interaction between Anaplastic Lymphoma Kinase (Alk) and NF1 in cognitive performance. In addition, pharmacologic inhibition of Alk improves cognitive performance in heterozygous NF1 mutant flies. In this study, we tested whether pharmacological inhibition of Alk in heterozygous NF1 mutant mice attenuates or rescues cognitive impairments. Cognitive impairment of spatial memory retention observed in heterozygous NF1 mutant mice was rescued by the Alk inhibitor. These data support the hypothesis that inhibition of Alk may cognitively benefit patients with Neurofibromatosis 1.
90%的神经纤维瘤病患者存在杂合型神经纤维瘤病1型（NF1）功能丧失突变，神经纤维瘤病是一种与致残性认知障碍相关的综合征。果蝇研究表明，间变性淋巴瘤激酶（Alk）与NF1在认知表现方面存在遗传相互作用。此外，对Alk的药理学抑制可改善杂合型NF1突变果蝇的认知表现。在本研究中，我们测试了对杂合型NF1突变小鼠进行Alk的药理学抑制是否能减轻或挽救认知障碍。Alk抑制剂挽救了杂合型NF1突变小鼠中观察到的空间记忆保持的认知障碍。这些数据支持以下假设：抑制Alk可能对神经纤维瘤病1型患者的认知有益。
