Anti-aggregation and fibril-destabilizing effects of sex hormones on alpha-synuclein fibrils in vitro.
The alpha-synuclein aggregation in the brain is the hallmark of Lewy body diseases, including Parkinson's disease and dementia with Lewy bodies, and multiple system atrophy. Some epidemiological studies have revealed that estrogen therapy reduces the risk of Parkinson's disease in females. We examined the effects of estriol, estradiol, estrone, androstenedione, and testosterone on the formation and destabilization of alpha-synuclein fibrils at pH 7.5 and 37 degrees C in vitro, using fluorescence spectroscopy with thioflavin S and electron microscopy. These sex hormones, especially estriol, significantly exert anti-aggregation and fibril-destabilizing effects; and hence, could be valuable preventive and therapeutic agents for alpha-synucleinopathies.
Hirohata
Mie
M
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Ono
Kenjiro
K
Morinaga
Akiyoshi
A
Ikeda
Tokuhei
T
Yamada
Masahito
M
D052160:Benzothiazoles; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004964:Estriol / Q000378:metabolism / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D016631:Lewy Bodies / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020961:Lewy Body Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008854:Microscopy, Electron; D015394:Molecular Structure; D009454:Neurofibrils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013050:Spectrometry, Fluorescence; D013739:Testosterone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D013844:Thiazoles / Q000737:chemistry; D051844:alpha-Synuclein / Q000187:drug effects* / Q000378:metabolism
D052160:Benzothiazoles; D012739:Gonadal Steroid Hormones; D018696:Neuroprotective Agents; D013844:Thiazoles; D051844:alpha-Synuclein; C009462:thioflavin T; D013739:Testosterone; D004958:Estradiol; D004964:Estriol