title: Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer's disease model.
abstract: Several lines of evidence suggest that neuregulin 1 (NRG1) signaling may influence cognitive function and neuropathology in Alzheimer's disease (AD). To test this possibility, full-length type I or type III NRG1 was overexpressed via lentiviral vectors in the hippocampus of line 41 AD mouse. Both type I and type III NRG1 improves deficits in the Morris water-maze behavioral task. Neuropathology was also significantly ameliorated. Decreased expression of the neuronal marker MAP2 and synaptic markers PSD95 and synaptophysin in AD mice was significantly reversed. Levels of Aβ peptides and plaques were markedly reduced. Furthermore, we showed that soluble ectodomains of both type I and type III NRG1 significantly increased expression of Aβ-degrading enzyme neprilysin (NEP) in primary neuronal cultures. Consistent with this finding, immunoreactivity of NEP was increased in the hippocampus of AD mice. These results suggest that NRG1 provides beneficial effects in candidate neuropathologic substrates of AD and, therefore, is a potential target for the treatment of AD.
authors: Clayton Foundation for Peptide Biology Laboratories, The Salk Institute, La Jolla, CA 92037, USA.
authors: Jiqing
authors: J
authors: Xu
authors: Clayton Foundation for Peptide Biology Laboratories, The Salk Institute, La Jolla, CA 92037, USA.
authors: Fred
authors: F
authors: de Winter
authors: Clayton Foundation for Peptide Biology Laboratories, The Salk Institute, La Jolla, CA 92037, USA.
authors: Catherine
authors: C
authors: Farrokhi
authors: Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093, USA.
authors: Edward
authors: E
authors: Rockenstein
authors: Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093, USA.
authors: Michael
authors: M
authors: Mante
authors: Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093, USA.
authors: Anthony
authors: A
authors: Adame
authors: Molecular Neurobiology Laboratories, The Salk Institute, La Jolla, CA 92037, USA.
authors: Jonathan
authors: J
authors: Cook
authors: Molecular Neurobiology Laboratories, The Salk Institute, La Jolla, CA 92037, USA.
authors: Xin
authors: X
authors: Jin
authors: Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093, USA.
authors: Eliezer
authors: E
authors: Masliah
authors: Clayton Foundation for Peptide Biology Laboratories, The Salk Institute, La Jolla, CA 92037, USA.
authors: Kuo-Fen
authors: KF
authors: Lee
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology / Q000523:psychology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003071:Cognition; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D018782:Maze Learning; D008822:Mice, Transgenic; D015260:Neprilysin / Q000378:metabolism; D020890:Neuregulin-1 / Q000502:physiology*; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D020890:Neuregulin-1; C490580:Nrg1 protein, rat; D015260:Neprilysin