Multiple sclerosis (MS) is an autoimmune disease characterized by myelin and axonal damage in the central nervous system (CNS). Glial scar which is a hallmark of MS contains repair inhibitory molecules including chondroitin sulfate proteoglycans (CSPGs). CSPGs inhibit repair of damaged area through various receptors including protein tyrosine phosphatase sigma (PTPσ). In the current study we use intracellular sigma peptide (ISP), an inhibitor of PTPσ signaling, in LPC-induced focal demyelination of mouse optic chiasm. ISP treatment resulted in decreased demyelination, reduced astrogliosis, and increased newly generated oligodendrocytes which subsequently led to enhanced remyelination. Analyzing of electrophysiological (as performed by visual evoked potential recording) and behavioral (performed by visual cliff test) outcomes showed that ISP-treatment improved the integrity of optic pathway as well as the visual acuity. When ISP was administrated only during the repair phase, histological, electrophysiological and behavioral studies showed its regenerative effect. Our results demonstrated the possibility of using ISP as a new strategy to inhibit PTPσ for myelin protection, myelin repair in demyelinated axons, and functional neural pathway conductivity restoration in patients suffering from MS.

中文翻译：

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使用细胞内sigma肽调节蛋白聚糖受体PTPσ可改善脱髓鞘性视交叉症小鼠的髓鞘再生和功能恢复。

多发性硬化症（MS）是一种自身免疫性疾病，其特征在于中枢神经系统（CNS）的髓磷脂和轴突损伤。胶质瘢痕是MS的标志，其包含修复抑制分子，包括硫酸软骨素蛋白聚糖（CSPG）。CSPG通过各种受体（包括蛋白酪氨酸磷酸酶sigma（PTPσ））抑制受损区域的修复。在当前的研究中，我们在LPC诱导的小鼠视交叉的局灶性脱髓鞘中使用细胞内sigma肽（ISP），PTPσ信号的抑制剂。ISP治疗导致脱髓鞘减少，星形胶质细胞减少和新生成的少突胶质细胞增多，随后导致髓鞘再生增强。对电生理学（通过视觉诱发电位记录执行）和行为（通过视觉悬崖测试执行）结果的分析表明，ISP治疗可改善视神经通路的完整性以及视敏度。当仅在修复阶段使用ISP时，组织学，电生理学和行为学研究表明其具有再生作用。我们的结果证明了使用ISP作为抑制PTPσ的新策略的可能性，以保护髓鞘质，保护脱髓鞘轴突中的髓鞘以及恢复MS患者的功能性神经通路传导性。