Pharmacological inhibition of Anaplastic Lymphoma Kinase rescues spatial memory impairments in Neurofibromatosis 1 mutant mice

Joseph B. Weiss, Sydney Weber, Tessa Marzulla, Jacob Raber

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)337-342
Number of pages6
JournalBehavioural Brain Research
Volume332
DOIs
StatePublished - Aug 14 2017

Keywords

  • Alk inhibitor
  • NF1
  • Neurofibromatosis
  • Spatial memory
  • Swim speed
  • Water maze

ASJC Scopus subject areas

  • Behavioral Neuroscience

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