Insulin, IGF-1 and GLP-1 signaling in neurodegenerative disorders: targets for disease modification?
Progress in Neurobiology. 2014-07-01; 118: 1-18
DOI: 10.1016/j.pneurobio.2014.02.005
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1. Prog Neurobiol. 2014 Jul;118:1-18. doi: 10.1016/j.pneurobio.2014.02.005. Epub
2014 Feb 28.
Insulin, IGF-1 and GLP-1 signaling in neurodegenerative disorders: targets for
disease modification?
Bassil F(1), Fernagut PO(1), Bezard E(2), Meissner WG(3).
Author information:
(1)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France.
(2)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; Service de Neurologie, CHU de Bordeaux, Pessac, France.
(3)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; Service de Neurologie, CHU de Bordeaux, Pessac, France.
Electronic address: .
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.
Copyright © 2014 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.pneurobio.2014.02.005
PMID: 24582776 [Indexed for MEDLINE]