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 journalArticle

3 Citations (Scopus)

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

Fingerprint

Neurofibromatosis 1
Pharmacology
Neurofibromatoses
Diptera
Drosophila
Spatial Memory
anaplastic lymphoma kinase
Inhibition (Psychology)
Mutation
Cognitive Dysfunction

Keywords

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

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Pharmacological inhibition of Anaplastic Lymphoma Kinase rescues spatial memory impairments in Neurofibromatosis 1 mutant mice. / Weiss, Joseph B.; Weber, Sydney; Marzulla, Tessa; Raber, Jacob.

In: Behavioural Brain Research, Vol. 332, 14.08.2017, p. 337-342.

Research output: Contribution to journalArticle

@article{a44b6efe0ec54b64bcf3a3717fc5b587,
title = "Pharmacological inhibition of Anaplastic Lymphoma Kinase rescues spatial memory impairments in Neurofibromatosis 1 mutant mice",
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.",
keywords = "Alk inhibitor, Neurofibromatosis, NF1, Spatial memory, Swim speed, Water maze",
author = "Weiss, {Joseph B.} and Sydney Weber and Tessa Marzulla and Jacob Raber",
year = "2017",
month = "8",
day = "14",
doi = "10.1016/j.bbr.2017.06.024",
language = "English (US)",
volume = "332",
pages = "337--342",
journal = "Behavioural Brain Research",
issn = "0166-4328",
publisher = "Elsevier",

}

TY - JOUR

T1 - Pharmacological inhibition of Anaplastic Lymphoma Kinase rescues spatial memory impairments in Neurofibromatosis 1 mutant mice

AU - Weiss, Joseph B.

AU - Weber, Sydney

AU - Marzulla, Tessa

AU - Raber, Jacob

PY - 2017/8/14

Y1 - 2017/8/14

N2 - 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.

AB - 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.

KW - Alk inhibitor

KW - Neurofibromatosis

KW - NF1

KW - Spatial memory

KW - Swim speed

KW - Water maze

UR - http://www.scopus.com/inward/record.url?scp=85021248329&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021248329&partnerID=8YFLogxK

U2 - 10.1016/j.bbr.2017.06.024

DO - 10.1016/j.bbr.2017.06.024

M3 - Article

C2 - 28629962

AN - SCOPUS:85021248329

VL - 332

SP - 337

EP - 342

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

ER -