Insulin, IGF-1 and GLP-1 signaling in neurodegenerative disorders: targets for disease modification?
Identifieur interne : 000772 ( Main/Exploration ); précédent : 000771; suivant : 000773Insulin, IGF-1 and GLP-1 signaling in neurodegenerative disorders: targets for disease modification?
Auteurs : Fares Bassil [France] ; Pierre-Olivier Fernagut [France] ; Erwan Bezard [France] ; Wassilios G. Meissner [France]Source :
- Progress in Neurobiology [ 0301-0082 ] ; 2014-06-30.
Abstract
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.
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DOI: 10.1016/j.pneurobio
Affiliations:
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Meissner</name><affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-259761" status="VALID"> <orgName>Université de Bordeaux</orgName> <orgName type="acronym">UB</orgName> <desc> <address> <addrLine>35, place Pey Berland - 33076 Bordeaux</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.u-bordeaux.fr/</ref> </desc></hal:affiliation><country>France</country></affiliation></author></analytic><idno type="DOI">10.1016/j.pneurobio</idno><series><title level="j">Progress in Neurobiology</title><idno type="ISSN">0301-0082</idno><imprint><date type="datePub">2014-06-30</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Aquitaine</li><li>Nouvelle-Aquitaine</li></region><settlement><li>Bordeaux</li></settlement><orgName><li>Université de Bordeaux</li></orgName></list><tree><country name="France"><region name="Nouvelle-Aquitaine"><name sortKey="Bassil, Fares" sort="Bassil, Fares" uniqKey="Bassil F" first="Fares" last="Bassil">Fares Bassil</name></region><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><name sortKey="Fernagut, Pierre Olivier" sort="Fernagut, Pierre Olivier" uniqKey="Fernagut P" first="Pierre-Olivier" last="Fernagut">Pierre-Olivier Fernagut</name><name sortKey="Meissner, Wassilios G" sort="Meissner, Wassilios G" uniqKey="Meissner W" first="Wassilios G" last="Meissner">Wassilios G. 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