Disease modifying effect of adiponectin in model of α‐synucleinopathies. (3rd July 2014)

• Record Type: Journal Article
• Authors: Sekiyama, Kazunari; Waragai, Masaaki; Akatsu, Hiroyasu; Sugama, Shuei; Takenouchi, Takato; Takamatsu, Yoshiki; Fujita, Masayo; Sekigawa, Akio; Rockenstein, Edward; Inoue, Satoshi; La Spada, Albert R.; Masliah, Eliezer; Hashimoto, Makoto
• Is Part Of: Annals of clinical and translational neurology. Volume 1:Number 7(2014)
• Page Start: 479
• Page End: 489
• Publication Date: 2014-07-03
• Subjects: Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1002/acn3.77
• Languages: English
• ISSNs: 2328-9503

Abstract

<abstract abstract-type="main" id="acn377-abs-0001"> <title>Abstract</title> <sec id="acn377-sec-0001" sec-type="section"> <title>Objective</title> <p>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 antidiabetes protein, in the pathogenesis of <italic>α</italic>‐synucleinopathies.</p> </sec> <sec id="acn377-sec-0002" sec-type="section"> <title>Methods</title> <p>Using biochemical and histological methods, we investigated autopsy brain of <italic>α</italic>‐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 <italic>α</italic>‐synucleinopathies.</p> </sec> <sec id="acn377-sec-0003" sec-type="section"> <title>Results</title> <p>We observed that APN is localized in Lewy bodies derived from <italic>α</italic>‐synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies. In neuronal cells expressing <italic>α</italic>‐synuclein (<italic>α</italic>S), aggregation of <italic>α</italic>S was suppressed by treatment with recombinant APN in an AdipoRI‐AMP kinase pathway‐dependent manner. Concomitantly, phosphorylation and release of <italic>α</italic>S were significantly decreased by APN, suggesting that APN may be antineurodegenerative. In transgenic mice expressing <italic>α</italic>S, 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 <italic>α</italic>S, might partly contribute to suppression of aggregation of <italic>α</italic>S by APN.</p> </sec> <sec id="acn377-sec-0004" sec-type="section"> <title>Interpretation</title> <p>Taken together, APN may suppress neurodegeneration through modification of the metabolic pathway, and could possess a therapeutic potential against <italic>α</italic>‐synucleinopathies.</p> </sec> </abstract>