Cell death discovery · 2023
Neuroprotection and axon regeneration by novel low-molecular-weight compounds through the modification of DOCK3 conformation.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Namekata Kazuhiko, Tsuji Naoki, Guo Xiaoli, Nishijima Euido, Honda Sari, Kitamura Yuta, Yamasaki Atsushi, Kishida Masamichi, Takeyama Jun, Ishikawa Hirokazu, Shinozaki Youichi, Kimura Atsuko, Harada Chikako, Harada Takayuki
Аннотация
Dedicator of cytokinesis 3 (DOCK3) is an atypical member of the guanine nucleotide exchange factors (GEFs) and plays important roles in neurite outgrowth. DOCK3 forms a complex with Engulfment and cell motility protein 1 (Elmo1) and effectively activates Rac1 and actin dynamics. In this study, we screened 462,169 low-molecular-weight compounds and identified the hit compounds that stimulate the interaction between DOCK3 and Elmo1, and neurite outgrowth in vitro. Some of the derivatives from the hit compound stimulated neuroprotection and axon regeneration in a mouse model of optic nerve injury. Our findings suggest that the low-molecular-weight DOCK3 activators could be a potential therapeutic candidate for treating axonal injury and neurodegenerative diseases including glaucoma.