A Leptin Fragment Mirrors the Cognitive Enhancing and Neuroprotective Actions of Leptin

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

Research output: Contribution to journalArticlepeer-review


A key pathology of Alzheimer's disease (AD) is amyloid β (Aβ) accumulation that 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.
Original languageEnglish
Pages (from-to)4769-4782
Number of pages14
JournalCerebral cortex (New York, N.Y. : 1991)
Issue number10
Publication statusPublished - 1 Oct 2016


  • Alzheimer Disease/physiopathology
  • Amyloid beta-Peptides/metabolism
  • Cell Death/drug effects
  • Cognition/drug effects
  • Hippocampus/metabolism
  • Humans
  • Leptin/metabolism
  • Memory/drug effects
  • Neuronal Plasticity/physiology
  • Neurons/metabolism
  • Peptide Fragments/metabolism
  • Synapses/drug effects


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