Leptin rescues neurons from Alzheimer’s disease-related pathways triggered by lipid burden

Greco, Steven J. and Perry, George and Ashford, J. Wesson and Hamzelou, Ashkan and Johnston, Jane M. and Tezapsidis, Nikolaos (2013) Leptin rescues neurons from Alzheimer’s disease-related pathways triggered by lipid burden. Advances in Alzheimer's Disease, 02 (01). pp. 31-39. ISSN 2169-2459

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Abstract

Adipocyte-derived leptin is a pleiotropic hormone implicated in control of lipid storage and mobilization, bone homeostasis, immune function and neuronal plasticity. Leptin has been shown to prevent accumulation of extracellular Aβ and hyperphosphorylation of tau in both cell culture and animal models. Herein an investigation was undertaken to test leptin’s ability to prevent the exacerbation/activation of AD-related pathways in neurons following their exposure to a high concentration of a variety of lipids. Specifically, cholesterol, oleic acid and/or ceramide were added to the media of cells resulting in decreased cellular viability and energy metabolism, and in increased tau phosphorylation and extracellular Aβ. Leptin increased viability, boosted cellular metabolism by activating AMP-activated protein kinase (AMPK) and the sirtuins (SIRT) and reduced tau phosphorylation and Aβ accumulation in a dose-dependent manner in response to select challenges. These findings demonstrate that leptin can attenuate the harmful effect of certain lipids that lead to exacerbation or activation of AD pathways. The study herein also provides the basis for a novel screening platform to define and identify a novel class of “metabolic” compounds addressing Alzheimer’s disease, based on a biological profile similar to leptin.

Item Type: Article
Subjects: ScienceOpen Library > Medical Science
Depositing User: Managing Editor
Date Deposited: 13 Apr 2023 05:46
Last Modified: 12 Sep 2024 04:23
URI: http://scholar.researcherseuropeans.com/id/eprint/968

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