TY - JOUR AB - Glutamate neurotoxicity has been implicated in the initiation and progression of various neurological and neurodegenerative disorders. Therefore, it is necessary to develop therapeutics for the treatment of patients with these devastating diseases. Mitochondrial fission plays an import role in the mediation of cell death and survival. The objective of the present study was to determine whether B355252, a phenoxythiophene sulfonamide derivative, reduces glutamate‑­induced cell death by inhibiting mitochondrial fission and the nuclear translocation of apoptosis‑inducing factor (AIF) in glutamate‑challenged HT22 neuronal cells. The results revealed that glutamate treatment led to large increases in the mitochondrial levels of the major fission proteins dynamin‑related protein 1 (Drp1) and mitochondrial fission 1 protein (Fis1), but only small elevations in the fusion proteins mitofusin 1 and 2 (Mfn1/2) and optic atrophy 1 (Opa1). In addition, glutamate toxicity disrupted mitochondrial reticular networks and increased the translocation of AIF to the nucleus. Pretreatment with B35525 reduced glutamate‑induced cell death and prevented the increases in the protein levels of Drp1, Fis1, Mfn1/2 and Opa1 in the mitochondrial fraction. More importantly, the architecture of the mitochondria was protected and nuclear translocation of AIF was completely inhibited by B35525. These findings suggest that the regulation of mitochondrial dynamics is central to the neuroprotective properties of B355252, and presents an attractive opportunity for potential development as a therapy for neurodegenerative disorders associated with mitochondria dysfunction. AD - Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), North Carolina Central University, Durham, NC 27707, USA AU - Zhang,Yuxin AU - Gliyazova,Nailya,S. AU - Li,P. Andy AU - Ibeanu,Gordon DA - 2021/03/01 DO - 10.3892/etm.2021.9652 IS - 3 JO - Exp Ther Med KW - B355252 arylthiophene phenoxythiophene glutamate neuronal cell death mitochondrial fission mitochondria dynamics apoptosis‑inducing factor PY - 2021 SN - 1792-0981 1792-1015 SP - 221 ST - Phenoxythiophene sulfonamide compound B355252 protects neuronal cells against glutamate‑induced excitotoxicity by attenuating mitochondrial fission and the nuclear translocation of AIF T2 - Experimental and Therapeutic Medicine TI - Phenoxythiophene sulfonamide compound B355252 protects neuronal cells against glutamate‑induced excitotoxicity by attenuating mitochondrial fission and the nuclear translocation of AIF UR - https://doi.org/10.3892/etm.2021.9652 VL - 21 ER -