TRO19622, a small cholesterol-like molecule, is a neuroregenerative and neuroprotective compound.
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Olesoxime (TRO 19622) exposure (ranging from 0.1 to 10 µM) 1 hour after plating significantly protects primary embryonic rat spinal MNs from cell death, with a 74±10% survival rate at 10 µM when supported by neurotrophic factors. Its EC50 for this effect is 3.2±0.2 µM. Besides preserving MN cell bodies, Olesoxime also promotes neurite outgrowth; at 1 µM, it enhances cell survival by 38% and increases neurite outgrowth per cell by 54%[1]. Olesoxime belongs to a novel class of cholesterol-oximes, targets outer mitochondrial membrane proteins, concentrates at mitochondria, and prevents oxidative stress-mediated permeability transition pore opening[2].
体内研究
Chronic administration of Olesoxime (3 or 30 mg/kg sc) to adult mice over two months is well-tolerated, showing no toxicity or adverse effects[1].
When treated orally for five days after a lesion, Olesoxime (TRO 19622) enhances motor neuron cell body survival in a dose-dependent fashion, achieving significant improvement at the highest dose of 100 mg/kg. At this dose, motor neuron survival rates are 29 ±2% (n=18), representing a 42% increase in survival compared to animals treated with a vehicle[3].
Rats treated with paclitaxel and given prophylactic doses of 3 mg/kg/d or 30 mg/kg/d olesoxime (TRO 19622) exhibited 239±17.6 and 247±14.4 intraepidermal nerve fibers (IENFs) per cm, respectively. These doses resulted in significantly less reduction compared to the 46% decrease observed in paclitaxel-treated rats receiving vehicle. Nonetheless, both doses led to decreases (25% and 22%) significantly distinct from the naïve control group [4].
体外研究
Olesoxime (TRO 19622) exposure (ranging from 0.1 to 10 µM) 1 hour after plating significantly protects primary embryonic rat spinal MNs from cell death, with a 74±10% survival rate at 10 µM when supported by neurotrophic factors. Its EC50 for this effect is 3.2±0.2 µM. Besides preserving MN cell bodies, Olesoxime also promotes neurite outgrowth; at 1 µM, it enhances cell survival by 38% and increases neurite outgrowth per cell by 54%[1].
Olesoxime belongs to a novel class of cholesterol-oximes, targets outer mitochondrial membrane proteins, concentrates at mitochondria, and prevents oxidative stress-mediated permeability transition pore opening[2].
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