Valdivia Anddre Osmar, Bhattacharya Sanjoy K
Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, Florida 33136.
Neuroscience Graduate Program, University of Miami, Miami, Florida 33136.
eNeuro. 2022 Jan 26;9(1). doi: 10.1523/ENEURO.0429-21.2022. Print 2022 Jan-Feb.
Protein hyperdeimination and deficiency of lyso-phospholipids (LPC 18:1) has been associated with the pathology of demyelinating disease in both humans and mice. We uncovered interesting biology of LPC 18:1, in which LPC 18:1 induced optic nerve function restoration through oligodendrocyte maturation and remyelination in mouse model systems. Our studies show LPC 18:1 protection against neuron-ectopic hyperdeimination and stimulation of oligodendrocyte maturation, while investigations recorded optic nerve function improvement following optic nerve injections of LPC 18:1, in contrast with LPC 18:0. Thus, just a change in a single bond renders a dramatic alternation in biological function. The incorporation of isobaric C13-histidine in newly synthesized myelin proteins and quantitative proteome shifts are consistent with remyelination underlying restoration in optic nerve function. These results suggest that exogenous LPC 18:1 may provide a therapeutic avenue for stemming vision loss in demyelinating diseases.
蛋白质超脱亚胺化和溶血磷脂（LPC 18:1）缺乏与人类和小鼠脱髓鞘疾病的病理过程相关。我们发现了LPC 18:1有趣的生物学特性，其中LPC 18:1在小鼠模型系统中通过少突胶质细胞成熟和髓鞘再生诱导视神经功能恢复。我们的研究表明LPC 18:1可防止神经元异位超脱亚胺化并刺激少突胶质细胞成熟，而研究记录了与LPC 18:0相比，视神经注射LPC 18:1后视神经功能得到改善。因此，仅仅一个单键的改变就会使生物学功能发生巨大变化。新合成的髓鞘蛋白中引入等压C13-组氨酸以及定量蛋白质组变化与视神经功能恢复背后的髓鞘再生一致。这些结果表明，外源性LPC 18:1可能为阻止脱髓鞘疾病中的视力丧失提供一条治疗途径。
