作者
Mychael V. Lourenco,Rudimar Luiz Frozza,Guilherme B. de Freitas,Hong Zhang,Grasielle C. Kincheski,Felipe C. Ribeiro,Rafaella Araújo Gonçalves,Julia R. Clarke,Danielle Beckman,Agnieszka Staniszewski,Hanna Berman,Lorena A. Guerra,Letícia Forny-Germano,Shelby E. Meier,Donna M. Wilcock,Jorge Marcondes de Souza,Soniza Vieira Alves-Leon,Vânia F. Prado,Jose F. Abisambra,Fernanda Tovar‐Moll,Paulo Mattos,Ottavio Arancio,Sérgio T. Ferreira,Fernanda G. De Felice
摘要
Defective brain hormonal signaling has been associated with Alzheimer's disease (AD), a disorder characterized by synapse and memory failure. Irisin is an exercise-induced myokine released on cleavage of the membrane-bound precursor protein fibronectin type III domain-containing protein 5 (FNDC5), also expressed in the hippocampus. Here we show that FNDC5/irisin levels are reduced in AD hippocampi and cerebrospinal fluid, and in experimental AD models. Knockdown of brain FNDC5/irisin impairs long-term potentiation and novel object recognition memory in mice. Conversely, boosting brain levels of FNDC5/irisin rescues synaptic plasticity and memory in AD mouse models. Peripheral overexpression of FNDC5/irisin rescues memory impairment, whereas blockade of either peripheral or brain FNDC5/irisin attenuates the neuroprotective actions of physical exercise on synaptic plasticity and memory in AD mice. By showing that FNDC5/irisin is an important mediator of the beneficial effects of exercise in AD models, our findings place FNDC5/irisin as a novel agent capable of opposing synapse failure and memory impairment in AD.