Format

Send to

Choose Destination
Cereb Cortex. 2017 Oct 1;27(10):4769-4782. doi: 10.1093/cercor/bhw272.

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

Author information

1
Division of Neuroscience, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, DundeeDD1 9SY, UK.
2
School of Psychology and Neuroscience, St Mary's Quad, University of St Andrews, St Andrews, FifeKY16 9TS, UK.

Abstract

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.

KEYWORDS:

AMPA receptor trafficking; Alzheimer's disease; amyloid beta; episodic memory; hippocampus; synaptic plasticity

PMID:
27600840
DOI:
10.1093/cercor/bhw272
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center