University Of Tasmania
152099 - Alterations in leptin signaling.pdf (1.61 MB)

Alterations in leptin signaling in amyotrophic lateral sclerosis (Als)

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posted on 2023-05-21, 11:27 authored by Ferrera donato, A, Contreras, A, Frago, LM, Chowen, JA, Carmen Fernandez-MartosCarmen Fernandez-Martos
Leptin has been suggested to play a role in amyotrophic lateral sclerosis (ALS), a fatal progressive neurodegenerative disease. This adipokine has previously been shown to be associated with a lower risk of ALS and to confer a survival advantage in ALS patients. However, the role of leptin in the progression of ALS is unknown. Indeed, our understanding of the mechanisms underlying leptin's effects in the pathogenesis of ALS is very limited, and it is fundamental to determine whether alterations in leptin's actions take place in this neurodegenerative disease. To characterize the association between leptin signaling and the clinical course of ALS, we assessed the mRNA and protein expression profiles of leptin, the long-form of the leptin receptor (Ob-Rb), and leptin-related signaling pathways at two different stages of the disease (onset and end-stage) in TDP-43(A315T) mice compared to age-matched WT littermates. In addition, at selected time-points, an immunoassay analysis was conducted to characterize plasma levels of total ghrelin, the adipokines resistin and leptin, and metabolic proteins (plasminogen activator inhibitor type 1 (PAI-1), gastric inhibitory peptide (GIP), glucagon-like peptide 1 (GLP-1), insulin and glucagon) in TDP-43(A315T) mice compared to WT controls. Our results indicate alterations in leptin signaling in the spinal cord and the hypothalamus on the backdrop of TDP-43-induced deficits in mice, providing new evidence about the pathways that could link leptin signaling to ALS.


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International Journal of Molecular Sciences










Wicking Dementia Research Education Centre



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Copyright 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://

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Expanding knowledge in the health sciences