Nibaldo C Inestrosa


Country: Chile


  1. Cisternas P, Martinez M, Ahima R, William Wong G, Inestrosa N. Modulation of Glucose Metabolism in Hippocampal Neurons by Adiponectin and Resistin. Mol Neurobiol. 2018;: pubmed publisher
    ..These data suggest that altered CNS levels of adipokines in the context of obesity may impact glucose metabolism in hippocampal neurons, brain region involved in learning and memory functions. ..
  2. Salazar P, Cisternas P, Martinez M, Inestrosa N. Hypothyroidism and Cognitive Disorders during Development and Adulthood: Implications in the Central Nervous System. Mol Neurobiol. 2018;: pubmed publisher
    ..The aim of this review is to describe the role of the thyroid hormones with focus in brain function and neurodegenerative disorders. ..
  3. Ramos Fernández E, Tapia Rojas C, Ramirez V, Inestrosa N. Wnt-7a Stimulates Dendritic Spine Morphogenesis and PSD-95 Expression Through Canonical Signaling. Mol Neurobiol. 2018;: pubmed publisher
    ..Together, our data strongly demonstrate that Wnt-dependent target gene transcription is essential to hippocampal synaptic plasticity. ..
  4. Inestrosa N, Tapia Rojas C, Griffith T, Carvajal F, Benito M, Rivera Dictter A, et al. Tetrahydrohyperforin prevents cognitive deficit, A? deposition, tau phosphorylation and synaptotoxicity in the APPswe/PSEN1?E9 model of Alzheimer's disease: a possible effect on APP processing. Transl Psychiatry. 2011;1:e20 pubmed publisher
    ..These findings indicate that IDN5706 ameliorates AD neuropathology and could be considered of therapeutic relevance in AD treatment. ..
  5. Lambert C, Cisternas P, Inestrosa N. Role of Wnt Signaling in Central Nervous System Injury. Mol Neurobiol. 2016;53:2297-311 pubmed publisher
    ..Because Wnt signaling is involved in several physiological processes, the putative positive role of its activation after injury could be the basis for novel therapeutic approaches to CNS injury. ..
  6. Codocedo J, Ríos J, Godoy J, Inestrosa N. Are microRNAs the Molecular Link Between Metabolic Syndrome and Alzheimer's Disease?. Mol Neurobiol. 2016;53:2320-38 pubmed publisher
    ..In this review, we summarize some of the relevant evidence that points to the role of miRNAs in metabolic syndrome (MetS) and AD and propose that miRNAs may be a molecular link in the complex relationship between both diseases. ..
  7. Inestrosa N, Varela Nallar L. Wnt signalling in neuronal differentiation and development. Cell Tissue Res. 2015;359:215-23 pubmed publisher
    ..In this review, we summarize the reported roles of Wnt signalling cascades in these processes with a particular emphasis on the role of Wnts in neuronal differentiation and development. ..
  8. Vargas J, Ahumada J, Arrázola M, Fuenzalida M, Inestrosa N. WASP-1, a canonical Wnt signaling potentiator, rescues hippocampal synaptic impairments induced by Aβ oligomers. Exp Neurol. 2015;264:14-25 pubmed publisher
    ..Moreover, we found that WASP-1 blocked Aβ aggregation in vitro and reduced pathological tau phosphorylation in vivo. These results indicate that targeting canonical Wnt signaling with WASP-1 could have value for treating AD. ..
  9. Rivera D, Lindsay C, Codocedo J, Carreño L, Cabrera D, Arrese M, et al. Long-Term, Fructose-Induced Metabolic Syndrome-Like Condition Is Associated with Higher Metabolism, Reduced Synaptic Plasticity and Cognitive Impairment in Octodon degus. Mol Neurobiol. 2018;: pubmed publisher
    ..Our results indicate that LT-FC induced several facets of MetS that eventually could trigger brain disorders, in particular, synaptic dysfunction and reduced cognition. ..

More Information


  1. Retamales Ortega R, Vio C, Inestrosa N. P2C-Type ATPases and Their Regulation. Mol Neurobiol. 2016;53:1343-54 pubmed publisher
    ..In this article, we discuss the functions, isoforms, and localization of P2C-type ATPases, describe some of their modulators, and discuss their implications in some diseases. ..
  2. Cisternas P, Salazar P, Serrano F, Montecinos Oliva C, Arredondo S, Varela Nallar L, et al. Fructose consumption reduces hippocampal synaptic plasticity underlying cognitive performance. Biochim Biophys Acta. 2015;1852:2379-90 pubmed publisher
    ..The overall information raises concerns about the risk imposed by excessive fructose consumption on the pathology of neurological disorders. ..
  3. request reprint
    Montecinos Oliva C, Schuller A, Parodi J, Melo F, Inestrosa N. Effects of tetrahydrohyperforin in mouse hippocampal slices: neuroprotection, long-term potentiation and TRPC channels. Curr Med Chem. 2014;21:3494-506 pubmed
    ..We propose that the effect of IDN5706 is mediated through activation of the TRPC3/6/7 channel subfamily. The unveiling of the drug's mechanism of action is a necessary step toward the clinical use of IDN5706 in Alzheimer's disease. ..
  4. Oliva C, Inestrosa N. A novel function for Wnt signaling modulating neuronal firing activity and the temporal structure of spontaneous oscillation in the entorhinal-hippocampal circuit. Exp Neurol. 2015;269:43-55 pubmed publisher
  5. Cisternas P, Lindsay C, Salazar P, Silva Alvarez C, Retamales R, Serrano F, et al. The increased potassium intake improves cognitive performance and attenuates histopathological markers in a model of Alzheimer's disease. Biochim Biophys Acta. 2015;1852:2630-44 pubmed publisher
    ..Together, our data support the idea that changes in diet, such as an increase in K(+) intake, may be important in the prevention of AD onset as a non-pharmacological therapy. ..
  6. Godoy J, Valdivieso A, Inestrosa N. Nicotine Modulates Mitochondrial Dynamics in Hippocampal Neurons. Mol Neurobiol. 2018;: pubmed publisher
  7. Bastías Candia S, Zolezzi J, Inestrosa N. Revisiting the Paraquat-Induced Sporadic Parkinson's Disease-Like Model. Mol Neurobiol. 2018;: pubmed publisher
    ..Similarly, we discuss the relevance of PD-like models developed using this agrochemical compound. ..
  8. Ríos J, Godoy J, Inestrosa N. Wnt3a ligand facilitates autophagy in hippocampal neurons by modulating a novel GSK-3β-AMPK axis. Cell Commun Signal. 2018;16:15 pubmed publisher
    ..Finally, these results have new implications regarding the role of Wnt signaling in the modulation of autophagy in neurons, with a possible role in the removal of accumulated intracellular proteins. ..
  9. Bastías Candia S, Braidy N, Zolezzi J, Inestrosa N. Teneurins and Alzheimer's disease: a suggestive role for a unique family of proteins. Med Hypotheses. 2015;84:402-7 pubmed publisher
    ..Herein, we aim to highlight the main characteristics of teneurins and propose, based on current knowledge of this family of proteins, an interesting review of their potential involvement in Alzheimer's disease. ..
  10. Inestrosa N, Arenas E. Emerging roles of Wnts in the adult nervous system. Nat Rev Neurosci. 2010;11:77-86 pubmed publisher
    ..Here, the latest insights into the function of Wnt signalling in the adult nervous system and therapeutic opportunities for neurodegenerative diseases such as Alzheimer's and Parkinson's disease are discussed. ..
  11. Serrano F, Tapia Rojas C, Carvajal F, Hancke J, Cerpa W, Inestrosa N. Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice. Mol Neurodegener. 2014;9:61 pubmed publisher
    ..Our results suggest that ANDRO could be used in a potential preventive therapy during AD progression. ..
  12. Godoy J, Ríos J, Zolezzi J, Braidy N, Inestrosa N. Signaling pathway cross talk in Alzheimer's disease. Cell Commun Signal. 2014;12:23 pubmed publisher
  13. request reprint
    Serrano F, Tapia Rojas C, Carvajal F, Cisternas P, Viayna E, Sola I, et al. Rhein-Huprine Derivatives Reduce Cognitive Impairment, Synaptic Failure and Amyloid Pathology in AβPPswe/PS-1 Mice of Different Ages. Curr Alzheimer Res. 2016;13:1017-29 pubmed
    ..These studies indicated that rhein-huprine derivatives with multiple properties might have interesting therapeutic potential for AD. ..
  14. Rivera D, Lindsay C, Codocedo J, Morel I, Pinto C, Cisternas P, et al. Andrographolide recovers cognitive impairment in a natural model of Alzheimer's disease (Octodon degus). Neurobiol Aging. 2016;46:204-20 pubmed publisher
    ..degus as a natural model in which to study both neural damage associated with aging processes and the behavioral and neuropathological hallmarks of aging-related diseases such as AD. ..
  15. Fuenzalida M, Espinoza C, Pérez M, Tapia Rojas C, Cuitino L, Brandan E, et al. Wnt signaling pathway improves central inhibitory synaptic transmission in a mouse model of Duchenne muscular dystrophy. Neurobiol Dis. 2016;86:109-20 pubmed publisher
    ..These results indicate that Wnt signaling modulates GABA synaptic efficacy and could be a promising novel target for DMD cognitive therapy. ..
  16. Godoy J, Lindsay C, Quintanilla R, Carvajal F, Cerpa W, Inestrosa N. Quercetin Exerts Differential Neuroprotective Effects Against H2O2 and Aβ Aggregates in Hippocampal Neurons: the Role of Mitochondria. Mol Neurobiol. 2017;54:7116-7128 pubmed publisher
  17. Codocedo J, Inestrosa N. Wnt-5a-regulated miR-101b controls COX2 expression in hippocampal neurons. Biol Res. 2016;49:9 pubmed publisher
    ..The biological processes induced by Wnt-5a in hippocampal neurons, involve the regulation of several miRNAs including miR-101b, which has the capacity to regulate several targets, including COX-2 in the central nervous system. ..
  18. Vallejo D, Codocedo J, Inestrosa N. Posttranslational Modifications Regulate the Postsynaptic Localization of PSD-95. Mol Neurobiol. 2017;54:1759-1776 pubmed publisher
    ..In the present work, we review the posttranslational modifications that regulate the synaptic localization of PSD-95 and describe their functional consequences. We also explore the signaling pathways that induce such changes. ..
  19. request reprint
    Bastías Candia S, Garrido A N, Zolezzi J, Inestrosa N. Recent Advances in Neuroinflammation Therapeutics: PPARs/LXR as Neuroinflammatory Modulators. Curr Pharm Des. 2016;22:1312-23 pubmed
  20. Codocedo J, Inestrosa N. Environmental control of microRNAs in the nervous system: Implications in plasticity and behavior. Neurosci Biobehav Rev. 2016;60:121-38 pubmed publisher
    ..In this review, we discuss how exposure to various EFs modulates the expression and function of several miRNAs in the nervous system and how this control determines adaptation to their environment, behavior and disease state. ..
  21. Salazar P, Cisternas P, Codocedo J, Inestrosa N. Induction of hypothyroidism during early postnatal stages triggers a decrease in cognitive performance by decreasing hippocampal synaptic plasticity. Biochim Biophys Acta. 2017;1863:870-883 pubmed publisher
    ..Our findings suggest that the induction of hypothyroidism in a young rat model alters numerous functions at the level of the hippocampus. ..
  22. Oliva C, Montecinos Oliva C, Inestrosa N. Wnt Signaling in the Central Nervous System: New Insights in Health and Disease. Prog Mol Biol Transl Sci. 2018;153:81-130 pubmed publisher
    ..Finally, we will address the possibility of Wnt signaling manipulation to treat those pathophysiological aspects. ..
  23. Cisternas P, Inestrosa N. Brain glucose metabolism: Role of Wnt signaling in the metabolic impairment in Alzheimer's disease. Neurosci Biobehav Rev. 2017;80:316-328 pubmed publisher
    ..Thus, in the present review, we discuss the antecedents that support the relationship between Wnt signaling and energy metabolism in the Alzheimer's disease. ..
  24. Parodi J, Montecinos Oliva C, Varas R, Alfaro I, Serrano F, Varas Godoy M, et al. Wnt5a inhibits K(+) currents in hippocampal synapses through nitric oxide production. Mol Cell Neurosci. 2015;68:314-22 pubmed publisher
    ..Together, our results show that Wnt5a increases NO production by acting on ROR2 receptors, which in turn inhibit Kv currents. These results reveal a novel mechanism by which Wnt5a may regulate the excitability of hippocampal neurons. ..
  25. Dinamarca M, Di Luca M, Godoy J, Inestrosa N. The soluble extracellular fragment of neuroligin-1 targets Aβ oligomers to the postsynaptic region of excitatory synapses. Biochem Biophys Res Commun. 2015;466:66-71 pubmed publisher
    ..To our knowledge, this is the first report of the interaction between this extracellular fragment of NL-1 and Aβo, strongly suggest that NL-1 facilitates the targeting of Aβo to the postsynaptic regions of excitatory synapses. ..
  26. Muñoz F, Godoy J, Cerpa W, Poblete I, Huidobro Toro J, Inestrosa N. Wnt-5a increases NO and modulates NMDA receptor in rat hippocampal neurons. Biochem Biophys Res Commun. 2014;444:189-94 pubmed publisher
    ..To the best of our knowledge, this is the first time that Wnt-5a signaling is related to NO production, which in turn increases NMDARs trafficking to the cell surface. ..
  27. Inestrosa N, Carvajal F, Zolezzi J, Tapia Rojas C, Serrano F, Karmelic D, et al. Peroxisome proliferators reduce spatial memory impairment, synaptic failure, and neurodegeneration in brains of a double transgenic mice model of Alzheimer's disease. J Alzheimers Dis. 2013;33:941-59 pubmed publisher
    ..We concluded that peroxisomal proliferation reduces various AD neuropathological markers and peroxisome proliferators may be considered as potential therapeutic agents against the disease. ..
  28. Inestrosa N, Montecinos Oliva C, Fuenzalida M. Wnt signaling: role in Alzheimer disease and schizophrenia. J Neuroimmune Pharmacol. 2012;7:788-807 pubmed publisher
    ..This review focuses on the relationship between Wnt signaling and its potential relevance for the treatment of neurodegenerative and neuropsychiatric diseases including AD and Schizophrenia. ..
  29. Godoy J, Arrázola M, Ordenes D, Silva Alvarez C, Braidy N, Inestrosa N. Wnt-5a ligand modulates mitochondrial fission-fusion in rat hippocampal neurons. J Biol Chem. 2014;289:36179-93 pubmed publisher
  30. Alfaro I, Varela Nallar L, Varas Godoy M, Inestrosa N. The ROR2 tyrosine kinase receptor regulates dendritic spine morphogenesis in hippocampal neurons. Mol Cell Neurosci. 2015;67:22-30 pubmed publisher
    ..Our results indicate a crucial role of the ROR2 in the formation and maturation of the postsynaptic dendritic spines in hippocampal neurons. ..
  31. Torres V, Inestrosa N. Vertebrate Presynaptic Active Zone Assembly: a Role Accomplished by Diverse Molecular and Cellular Mechanisms. Mol Neurobiol. 2018;55:4513-4528 pubmed publisher
  32. Godoy J, Zolezzi J, Inestrosa N. INT131 increases dendritic arborization and protects against A? toxicity by inducing mitochondrial changes in hippocampal neurons. Biochem Biophys Res Commun. 2017;490:955-962 pubmed publisher
    ..Our results suggest that INT131, a drug that has been shown to be safe and effective in metabolic disorders, may constitute a new therapeutic alternative for AD. ..
  33. Tapia Rojas C, Lindsay C, Montecinos Oliva C, Arrázola M, Retamales R, Bunout D, et al. Is L-methionine a trigger factor for Alzheimer's-like neurodegeneration?: Changes in Aβ oligomers, tau phosphorylation, synaptic proteins, Wnt signaling and behavioral impairment in wild-type mice. Mol Neurodegener. 2015;10:62 pubmed publisher
    ..Taken together, the results of our study indicate that an L-methionine-enriched diet causes neurotoxic effects in vivo and might contribute to the appearance of Alzheimer's-like neurodegeneration. ..
  34. Cisternas P, Salazar P, Silva Alvarez C, Barros L, Inestrosa N. Activation of Wnt Signaling in Cortical Neurons Enhances Glucose Utilization through Glycolysis. J Biol Chem. 2016;291:25950-25964 pubmed
    ..Together, our results suggest that Wnt signaling stimulates glucose utilization in cortical neurons through glycolysis to satisfy the high energy demand of these cells. ..
  35. Ramirez V, Ramos Fernández E, Henriquez J, Lorenzo A, Inestrosa N. Wnt-5a/Frizzled9 Receptor Signaling through the G?o-G?? Complex Regulates Dendritic Spine Formation. J Biol Chem. 2016;291:19092-107 pubmed publisher
    ..Our findings reveal that FZD9 and heterotrimeric G proteins regulate Wnt-5a signaling and dendritic spines in cultured hippocampal neurons. ..
  36. Rivera D, Inestrosa N, Bozinovic F. On cognitive ecology and the environmental factors that promote Alzheimer disease: lessons from Octodon degus (Rodentia: Octodontidae). Biol Res. 2016;49:10 pubmed publisher
  37. Inestrosa N, Godoy J, Vargas J, Arrázola M, Ríos J, Carvajal F, et al. Nicotine prevents synaptic impairment induced by amyloid-? oligomers through ?7-nicotinic acetylcholine receptor activation. Neuromolecular Med. 2013;15:549-69 pubmed publisher
    ..Activation of the ?7-nAChR/PI3K signaling pathway and its cross-talk with the Wnt signaling pathway might well be therapeutic targets for potential AD treatments. ..