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| 1 | Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide显示文摘Long-acting glucagon-like peptide-1(GLP-1) analogues marketed for type 2 diabetes(T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2 D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors(GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions(e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2 D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation(thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2 D, stroke and Alzheimer disease(AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia inhibition, behavior and cognition, and in AD biomarkers. Herein, we discuss the GLP-1 action through the gut-brain axis, the hormone's regulation of some autonomic functions and liraglutide's neuroprotective potential. | Emanuel Monteiro Candeias Inês Carolina Sebastio Susana Maria Cardoso Sónia Catarina Correia Cristina Isabel Carvalho Ana Isabel Plácido Maria Sancha Santos Catarina Resende Oliveira Paula Isabel Moreira Ana Isabel Duarte | 2015 | World Journal of Diabetes2015，6，6： | 9 |
| 2 | Decreases in commu- nity viral load are accompanied by reductions in new HIV infections in San Francisco显示文摘 | Das M Chu PL Santos GM | 2010 | PLoS ONE2010，5，11： | 1 |
| 3 | Effects of oleanolic acid on pulmonary morphofunctional and biochemical variables in experimental acute lung injury显示文摘 | Santos RS Silva PL Oliveira GP | 2011 | Respir Physiol Neurobiol2011，179，2： | 1 |
| 4 | Lead-210 and polonium-210 concentrations in some species of marine molluscs显示文摘 | Gouvea RC Santos PL Dutra IR | 1992 | Sci Total [LL]Environ1992，112，23： | 1 |
| 5 | Relations of circulating C - reactive protein to progression of aortic - value stenosis显示文摘 | Sanchez PL Santos JL Kaski JC | 2006 | Am J Cardiol2006，97，1： | 1 |
| 6 | Clinical quality improvement: eliminating unplanned extubation in the CCU 显示文摘 | Chia PL Santos DR Tan TC | 2013 | Int J Health Care Qual Assur2013，26，7： | 1 |
| 7 | Systemic toxicity of levobupivacaine,bupiva-caine,and ropivacaineduring continuous intravenous infusion to non -pregnant and pregnant ewes显示文摘 | DeAmras Pl | 2001 | Anesthesiol2001，95，5： | 1 |
| 8 | Incomplete mandibular fracture after lateralization of the inferior alveolar nerve for implant placement显示文摘 | Dos Santos PL Gaujac C Shinohara EH | | 0，，03： | 1 |
| 9 | In vitro analysis of anionic collagen scaffolds for bone repair显示文摘 | Moreira PL An YH Santos AR Jr | 2004 | J Biomed Mater Res2004，1571，2： | 1 |
| 10 | Bone substitutes for peri-implant defects of postextraction implants显示文摘 | Santos PL Gulinelli JL Telles Cda S | 2013 | Int J Biomater2013，2013，30： | 1 |
| 11 | Maxil ary bone defect reconstruction using porous polyethylene implants显示文摘 | Dos Santos PL Santiago JF Ponzoni D | | 0，，06： | 1 |
| 12 | Hearing impairment in Dutch patients with connexin 26 (GJB2) and connexin 30 (GJB6) mutatians 显示文摘 | Santos RL Aulchenko YS Huygen PL | 2005 | Int J Pediatr Otorhinolaryngol2005，69，2： | 1 |
| 13 | Drillstring vibrationand wellbore instability显示文摘 | Plácido J C R Santos H M R Galeano Y D | 2002 | Journal of Energy ResourcesTechnology2002，124，4： | 1 |
| 14 | Systemic toxicity of leovbupivacaine, bupivacaine, and ropivacaine during continuous intravenous infusion to nonpregnant and pregnant ewes显示文摘 | Santos AC De Armas PL | 2001 | Anesthesiology2001，95，5： | 1 |
| 15 | Systemic toxicity of levobupivacaine,bupivacaine,and ropivacaine during continuous intravenous infusion to nonpregnant and pregnant ewes显示文摘 | Santos AC DeArmas Pl | 2001 | Anesthesiology2001，95，12： | 1 |
| 16 | Relations of circulating C-reactive protein to progression of aortic-value stenosis显示文摘 | Sanchez PL Santos JL Kaski JC | 2006 | Am J Cardiol2006，97，1： | 1 |
| 17 | Impact of pressure profile and duration of recruitment maneuvers on morphofunctional and biochemical variables in experimental lung injury显示文摘 | Silva PL Moraes L Santos RS | | 0，，： | 1 |
| 18 | Incomplete mandibular fracture after lateralization of the inferior alveolar nerve for implant placement显示文摘 | dos Santos PL Gaujac C Shinohara EH | 2013 | J Craniofac Surg2013，24，3： | 1 |
| 19 | Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco 显示文摘 | Das M Chu PL Santos GM | 2010 | PLoS ONE2010，5，11： | 1 |
| 20 | Comparative analysis of 2-flap designs for extraction of mandibular third molar显示文摘 | Silva JL Jardim EC dos Santos PL | 2011 | Craniofac Surg2011，22，3： | 1 |
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