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.

INTERPRETATION:

Taken together, APN may suppress neurodegeneration through modification of the metabolic pathway, and could possess a therapeutic potential against α-synucleinopathies.

• Authors: Kazunari Sekiyama, Masaaki Waragai, Hiroyasu Akatsu, Shuei Sugama, Takato Takenouchi, Yoshiki Takamatsu, Masayo Fujita, Akio Sekigawa, Edward Rockenstein, Satoshi Inoue, Albert R La Spada, Eliezer Masliah, Makoto Hashimoto
• Journal: Annals of clinical and translational neurology (Ann Clin Transl Neurol) Vol. 1 Issue 7 Pg. 479-489 (Jul 03 2014) ISSN: 2328-9503 [Print] United States
• PMID: 25126588 (Publication Type: Journal Article)