Neuron · 2024
Imaging α-synuclein pathologies in animal models and patients with Parkinson's and related diseases.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Endo Hironobu, Ono Maiko, Takado Yuhei, Matsuoka Kiwamu, Takahashi Manami, Tagai Kenji, Kataoka Yuko, Hirata Kosei, Takahata Keisuke, Seki Chie, Kokubo Naomi, Fujinaga Masayuki, Mori Wakana, Nagai Yuji, Mimura Koki, Kumata Katsushi, Kikuchi Tatsuya, Shimozawa Aki, Mishra Sushil K, Yamaguchi Yoshiki, Shimizu Hiroshi, Kakita Akiyoshi, Takuwa Hiroyuki, Shinotoh Hitoshi, Shimada Hitoshi, Kimura Yasuyuki, Ichise Masanori, Suhara Tetsuya, Minamimoto Takafumi, Sahara Naruhiko, Kawamura Kazunori, Zhang Ming-Rong, Hasegawa Masato, Higuchi Makoto
Аннотация
Deposition of α-synuclein fibrils is implicated in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), while in vivo detection of α-synuclein pathologies in these illnesses has been challenging. Here, we have developed a small-molecule ligand, C05-05, for visualizing α-synuclein deposits in the brains of living subjects. In vivo optical and positron emission tomography (PET) imaging of mouse and marmoset models demonstrated that C05-05 captured a dynamic propagation of fibrillogenesis along neural pathways, followed by disruptions of these structures. High-affinity binding of 18F-C05-05 to α-synuclein aggregates in human brain tissues was also proven by in vitro assays. Notably, PET-detectable 18F-C05-05 signals were intensified in the midbrains of PD and DLB patients as compared with healthy controls, providing the first demonstration of visualizing α-synuclein pathologies in these illnesses. Collectively, we propose a new imaging technology offering neuropathology-based translational assessments of PD and allied disorders toward diagnostic and therapeutic research and development.