title: Disease-Modifying Effect of Adiponectin in Model of α-Synucleinopathies.
abstract: OBJECTIVE
  Growing evidence suggests that neurodegenerative diseases are associated with metabolic disorders, but the mechanisms are still unclear. Better comprehension of this issue might provide a new strategy for treatment of neurodegenerative diseases. We investigated possible roles of adiponectin (APN), the anti-diabetes protein, in the pathogenesis of α-synucleinopathies.
  
  
  METHODS
  Using biochemical and histological methods, we investigated autopsy brain of α-synucleinopathies including Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and analyzed the effects of APN in cellular and in mouse models of α-synucleinopathies.
  
  
  RESULTS
  We observed that APN is localized in Lewy bodies derived from α-synucleinopathies such as Parkinson's disease and dementia with Lewy bodies. In neuronal cells expressing α-synuclein (αS), aggregation of αS was suppressed by treatment with recombinant APN in an AdipoRI-AMP kinase pathway-dependent manner. Concomitantly, phosphorylation and release of αS were significantly decreased by APN, suggesting that APN may be antineurodegenerative. In transgenic mice expressing αS, both histopathology and movement disorder were significantly improved by intranasal treatment with globular APN when the treatment was initiated in the early stage of the disease. In a mouse model, reduced levels of guanosine- and inosine- monophosphates, both of which are potential stimulators of aggregation of αS, might partly contribute to suppression of aggregation of αS by APN.
  
  
  CONCLUSIONS
  Taken together, APN may suppress neurodegeneration through modification of the metabolic pathway, and could possess a therapeutic potential against α-synucleinopathies.
authors.affiliation: Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sekiyama
authors.affiliation: Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Waragai
authors.affiliation: Choju Medical Institute, Fukushimura Hospital, Aichi 441-8124, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.affiliation: Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8602, Japan.
authors.forename: Shuei
authors.initials: S
authors.lastname: Sugama
authors.affiliation: Division of Animal Sciences, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8634, Japan.
authors.forename: Takato
authors.initials: T
authors.lastname: Takenouchi
authors.affiliation: Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Takamatsu
authors.affiliation: Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Sekigawa
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0624, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.affiliation: Department of Anti-Aging Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 156-0057, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Division of Genetics, Department of Pediatrics, Department of Cellular and Molecular Medicine, the Institute for Genomic Medicine, and the Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92037, USA ; Rady Children's Hospital, San Diego, CA 92123, USA.
authors.forename: Albert R
authors.initials: AR
authors.lastname: La Spada
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0624, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.affiliation: Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hashimoto