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W.Meissner , F Bassil et al. dans Progress in Neurobiology

l'insuline: des effets prometteurs sur les maladies neurodégénératives...

Le 14 avril 2014

Insulin, IGF-1 and GLP-1 signaling in neurodegenerative disorders: Targets for disease modification ?
Bassil F, Fernagut PO, Bezard E, Meissner WG.
Prog Neurobiol. 2014 Feb 28. pii: S0301-0082(14)00029-X. doi: 10.1016/j.pneurobio.2014.02.005. [Epub ahead of print] Review. 




Wassilios Meissner: Les récepteurs à l’insuline, à l’insulin-like growth factor-1 (IGF-1) et au glucagon-like peptide-1 (GLP-1), impliqués dans le contrôle de la glycémie dans les tissus périphériques, sont également exprimés dans le cerveau, y compris dans la substance noire. Des preuves scientifiques croissantes suggèrent que le dysfonctionnement des voies de signalisation récepteur à l’insuline/IGF-1 et au GLP-1 contribue à la perte progressive des neurones dans la maladie d'Alzheimer (MA) et la maladie de Parkinson (MP). Ces résultats ont conduit à de nombreuses études dans des modèles précliniques ciblant ces voies avec des antidiabétiques oraux, actuellement utilisés pour le traitement des patients diabétiques.


Ces études ont montré que l'administration de l'insuline, de l'IGF-1 ou des agonistes GLP-1 a des effets positifs sur le comportement et sur des marqueurs anatomo-pathologiques de la neurodégénérescence. Plusieurs études cliniques de preuve de concept sont en cours, tentant de traduire ces résultats précliniques encourageants en traitement pour les patients atteints de MA ou de MP.

Notre article de revue inclut (i) une vue d'ensemble des études précliniques ciblant la signalisation récepteur à l’insuline/IGF-1 et au GLP-1 pour le traitement de la MA et MP, (ii) les résultats préliminaires des essais cliniques qui ont utilisé des antidiabétiques oraux pour le traitement des patients Alzheimer ou parkinsoniens, et (iii) des considérations importantes pour une réussite de la translation des résultats précliniques dans de futurs traitements pour les patients atteints de MA et MP.


 

Wassilios Meissner:

Insulin, insulin growth factor-1 (IGF-1) and glucagon-like peptide-1 (GLP-1) play a major role in body homeostasis and glucose regulation, while their receptors are also expressed in the brain. Growing evidence suggests that dysfunction of these pathways contribute to the progressive loss of neurons in Alzheimer’s disease (AD) and Parkinson’s disease (PD), the two most frequent neurodegenerative disorders. These findings have led to numerous studies in preclinical models of neurodegenerative disorders targeting insulin/IGF-1 and GLP-1 signaling with currently available anti-diabetic drugs.
These studies have shown that administration of insulin, IGF-1 and GLP-1 agonists has positive effects on behavioral outcomes and surrogate markers of neurodegeneration.
Several clinical proof-of-concept studies are currently underway that attempt to translate these encouraging preclinical results to patients suffering from AD and PD. In our review, we provide (i) a comprehensive overview of preclinical studies targeting insulin/IGF-1 or GLP-1 signaling for treating AD and PD, (ii) detail the design and preliminary results of clinical trials that have used anti-diabetics for treating AD and PD patients, and (iii) close with considerations relevant for the successful translation of encouraging preclinical results into future treatments for patients with AD and PD.



Abstract pubMed

Insulin and Insulin Growth Factor-1 (IGF-1) play a major role in body homeostasis and glucose regulation. They also have paracrine/autocrine functions in the brain. The Insulin/IGF-1 signaling pathway contributes to the control of neuronal excitability, nerve cell metabolism and cell survival. Glucagon like peptide-1 (GLP-1), known as an insulinotropic hormone has similar functions and growth like properties as insulin/IGF-1. Growing evidence suggests that dysfunction of these pathways contribute to the progressive loss of neurons in Alzheimer's disease (AD) and Parkinson's disease (PD), the two most frequent neurodegenerative disorders. These findings have led to numerous studies in preclinical models of neurodegenerative disorders targeting insulin/IGF-1 and GLP-1 signaling with currently available anti-diabetics. These studies have shown that administration of insulin, IGF-1 and GLP-1 agonists reverses signaling abnormalities and has positive effects on surrogate markers of neurodegeneration and behavioral outcomes. Several proof-of-concept studies are underway that attempt to translate the encouraging preclinical results to patients suffering from AD and PD. In the first part of this review, we discuss physiological functions of insulin/IGF-1 and GLP-1 signaling pathways including downstream targets and receptors distribution within the brain. In the second part, we undertake a comprehensive overview of preclinical studies targeting insulin/IGF-1 or GLP-1 signaling for treating AD and PD. We then detail the design of clinical trials that have used anti-diabetics for treating AD and PD patients. We close with future considerations that treat relevant issues for successful translation of these encouraging preclinical results into treatments for patients with AD and PD.
http://www.sciencedirect.com/science/article/pii/S030100821400029X

1er Auteur


Fares Bassil
PhD Institut des Maladies Neurodegeneratives 
INSTITUTE OF NEURODEGENERATIVE DISEASES
Bordeaux


Université Bordeaux 2

Master's degree, Neuropsychopharmacology
2011 – 2012


Lebanese University

Bachelor's degree, Life and Earth Sciences
2007 – 2010