Brain insulin, insulin-like growth factor 1 and glucagon-like peptide 1 signalling in Alzheimer's disease.
Ferreira ST; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Journal of neuroendocrinology [J Neuroendocrinol] 2021 Apr; Vol. 33 (4), pp. e12959. Date of Electronic Publication: 2021 Mar 19.
Typ publikacji :
Journal Article; Review
Imprint Name(s) :
Publication: <2010->: Malden, MA : Wiley & Sons
Original Publication: Eynsham, Oxon, UK : Oxford University Press, c1989-
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Grant Information :
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro; Instituto Nacional de Ciência e Tecnologia de Neurociência Translacional; Conselho Nacional de Desenvolvimento Científico e Tecnológico
Contributed Indexing :
Keywords: Aβ oligomers; dementia; incretins; insulin resistance
Entry Date(s) :
Date Created: 20210319 Latest Revision: 20210419
Update Code :
Although the brain was once considered an insulin-independent organ, insulin signalling is now recognised as being central to neuronal health and to the function of synapses and brain circuits. Defective brain insulin signalling, as well as related signalling by insulin-like growth factor 1 (IGF-1), is associated with neurological disorders, including Alzheimer's disease, suggesting that cognitive impairment could be related to a state of brain insulin resistance. Here, I briefly review key epidemiological/clinical evidence of the association between diabetes, cognitive decline and AD, as well as findings of reduced components of insulin signalling in AD brains, which led to the initial suggestion that AD could be a type of brain diabetes. Particular attention is given to recent studies illuminating mechanisms leading to neuronal insulin resistance as a key driver of cognitive impairment in AD. Evidence of impaired IGF-1 signalling in AD is also examined. Finally, we discuss potentials and possible limitations of recent and on-going therapeutic approaches based on our increased understanding of the roles of brain signalling by insulin, IGF-1 and glucagon-like peptide 1 in AD.
(© 2021 British Society for Neuroendocrinology.)