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Rhizolutin directly dissociates Aβ and tau aggregates and reduces apoptosis/inflammation related to Alzheimer’s disease
Author(s) -
Shin Jisu,
Kwon Yun,
Nam Kwangho,
An Joon Soo,
Yang SeungHoon,
Hong SeongHeon,
Bae Munhyung,
Moon Kyuho,
Cho Yakdol,
Woo Jiwan,
Park Keunwan,
Kim Kyeonghwan,
Shin Jongheon,
Kim ByungYong,
Kim YoungSoo,
Oh DongChan
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.049661
Subject(s) - neuroinflammation , inflammation , apoptosis , neuroscience , genetically modified mouse , tau pathology , programmed cell death , hippocampal formation , microglia , atrophy , microbiology and biotechnology , amyloid (mycology) , transgene , disease , in vitro , chemistry , alzheimer's disease , biology , medicine , pathology , immunology , biochemistry , gene
Background Alzheimer’s disease (AD) is characterized by the aggregation of amyloid‐β (Aβ) and tau, leading to neuronal cell death, neuroinflammation, and brain atrophy. As Aβ and tau aggregates are observed in the brain decades before the onset of cognitive symptoms, clearance of these aggregates has been widely accepted for AD treatments. Method Through the unbiased screening against the natural product libraries, rhizolutin was selected and its regulatory effects on Aβ and tau aggregation were validated by thioflavin T assays. Clearance of Aβ plaques was observed in APP/PS1 double transgenic AD model mice and subsequent analyses regarding apoptosis and inflammation were conducted using neuronal and glial cell lines. Result Rhizolutin‐treated AD model mice significantly decreased hippocampal Aβ plaques. Additionally, rhizolutin effectively inhibited the aggregation of Aβ and tau in vitro , more importantly, dissociated both aggregates, thereby reducing Aβ‐induced apoptosis and inflammation in neuronal and glial cells. Conclusion Our findings reveal that a unique chemical rhizolutin regulates both Aβ and tau at the same time by therapeutic and preventive approaches, representing its novel structure is attractive for AD drug discovery.