The Adiponectin Homolog Osmotin Enhances Neurite Outgrowth and Synaptic Complexity via AdipoR1/NgR1 Signaling in Alzheimer's Disease

Mol Neurobiol. 2018 Aug;55(8):6673-6686. doi: 10.1007/s12035-017-0847-1. Epub 2018 Jan 15.


Alzheimer's disease is a major neurodegenerative disease characterized by memory loss and cognitive deficits. Recently, we reported that osmotin, which is a homolog of adiponectin, improved long-term potentiation and cognitive functions in Alzheimer's disease mice. Several lines of evidence have suggested that Nogo-A and the Nogo-66 receptor 1 (NgR1), which form a complex that inhibits long-term potentiation and cognitive function, might be associated with the adiponectin receptor 1 (AdipoR1), which is a receptor for osmotin. Here, we explore whether osmotin's effects on long-term potentiation and memory function are associated with NgR1 signaling via AdipoR1 in Alzheimer's disease. Osmotin reduced the expression of NgR1 without affecting Nogo-A expression. Furthermore, osmotin inhibited NgR1 signaling by prohibiting the formation of the Nogo-A and NgR1 ligand-receptor complex, resulting in enhanced neurite outgrowth; these effects disappeared in the presence of AdipoR1 interference. In addition, osmotin increased the expression of the pre- and postsynaptic markers synaptophysin and PSD-95, as well as the activation of the memory-associated markers AMPA receptor and CREB; these effects occurred in an AdipoR1- and NgR1-dependent manner. Osmotin was also found to enhance dendritic complexity and spine density in the hippocampal region of Alzheimer's disease mouse brains. These results suggest that osmotin can enhance neurite outgrowth and synaptic complexity through AdipoR1 and NgR1 signaling, implying that osmotin might be an effective therapeutic agent for Alzheimer's disease and that AdipoR1 might be a crucial therapeutic target for neurodegenerative diseases such as Alzheimer's.

Keywords: Adiponectin receptor 1; Alzheimer’s disease; Neurite outgrowth; Nogo-66 receptor 1; Osmotin; Synaptic complexity.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Biomarkers / metabolism
  • Brain / pathology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Humans
  • Male
  • Memory / drug effects
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuronal Outgrowth / drug effects*
  • Nogo Proteins / genetics
  • Nogo Proteins / metabolism
  • Nogo Receptor 1 / metabolism*
  • Plant Proteins / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Adiponectin / metabolism*
  • Signal Transduction*
  • Synapses / drug effects
  • Synapses / metabolism*


  • Amyloid beta-Peptides
  • Biomarkers
  • Nogo Proteins
  • Nogo Receptor 1
  • Plant Proteins
  • RNA, Messenger
  • Receptors, Adiponectin
  • osmotin protein, Nicotiana tabacum