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A leptin fragment mirrors the cognitive enhancing and neuroprotective actions of leptin

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Yasaman Malekizadeh, Alison Holiday, Devon Redfearn, James A. Ainge, Gayle Doherty, Jenni Harvey

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Abstract

A key pathology of Alzheimer’s disease (AD) is amyloid β (Aβ) accumulation which triggers synaptic impairments and neuronal death. Metabolic disruption is common in AD and recent evidence implicates impaired leptin function in AD. Thus the leptin system may be a novel therapeutic target in AD. Indeed, leptin has cognitive enhancing properties and it prevents the aberrant effects of Aβ on hippocampal synaptic function and neuronal viability. However as leptin is a large peptide, development of smaller leptin-mimetics may be the best therapeutic approach. Thus, we have examined the cognitive enhancing and neuroprotective properties of known bioactive leptin fragments. Here we show that the leptin (116-130) fragment, but not leptin (22-56), mirrored the ability of leptin to promote AMPA receptor trafficking to synapses and facilitate activity-dependent hippocampal synaptic plasticity. Administration of leptin (116-130) also mirrored the cognitive enhancing effects of leptin as it enhanced performance in episodic-like memory tests. Moreover, leptin (116-130) prevented hippocampal synaptic disruption and neuronal cell death in models of amyloid toxicity. These findings establish further the importance of the leptin system as a therapeutic target in AD.
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Original languageEnglish
Pages (from-to)4769–4782
JournalCerebral Cortex
Volume27
Issue number10
Early online date6 Sep 2016
DOIs
Publication statusPublished - 1 Oct 2017

    Research areas

  • Hippocampus, Synaptic plasticity, Amyloid beta, AMPA receptor trafficking, Episodic memory, Alzheimer’s disease

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