小柯机器人

美国哈佛医学院Clotilde Lagier-Tourenne等研究人员合作发现，stathmin-2缺失会导致神经丝依赖性轴突塌陷，从而导致运动和感觉神经失调。2023年11月23日，《自然—神经科学》杂志在线发表了这项成果。

研究人员表示，编码stathmin-2蛋白（又称SCG10）的人类STMN2基因的mRNA转录本会受到TAR DNA结合蛋白43（TDP-43）功能丧失的严重影响。后者是包括肌萎缩性脊髓侧索硬化症（ALS）在内的多种神经退行性疾病的特征。

研究人员采用了多种方法，包括瞬时反义寡核苷酸介导的抑制、衰老小鼠体内持续的shRNA诱导的缺失以及种系缺失。结果表明，stathmin-2在建立和维持依赖神经丝的轴浆组织中发挥着重要作用，而轴浆组织对于保持髓鞘化大直径轴突的口径和传导速度至关重要。成年小鼠体内stathmin-2的持续缺失会导致肌萎缩性脊髓侧索硬化症的病理变化，包括神经丝间距缩小、轴突口径塌陷导致外层髓鞘撕裂、传导速度降低、进行性运动和感觉障碍以及肌肉去神经支配。这些发现加强了恢复stathmin-2作为治疗ALS和其他TDP-43依赖性神经退行性疾病的有望方法。

附：英文原文

Title: Stathmin-2 loss leads to neurofilament-dependent axonal collapse driving motor and sensory denervation

Author: Lpez-Erauskin, Jone, Bravo-Hernandez, Mariana, Presa, Maximiliano, Baughn, Michael W., Melamed, Zeev, Beccari, Melinda S., Agra de Almeida Quadros, Ana Rita, Arnold-Garcia, Olatz, Zuberi, Aamir, Ling, Karen, Platoshyn, Oleksandr, Nio-Jara, Elkin, Ndayambaje, I. Sandra, McAlonis-Downes, Melissa, Cabrera, Larissa, Artates, Jonathan W., Ryan, Jennifer, Hermann, Anita, Ravits, John, Bennett, C. Frank, Jafar-Nejad, Paymaan, Rigo, Frank, Marsala, Martin, Lutz, Cathleen M., Cleveland, Don W., Lagier-Tourenne, Clotilde

Issue&Volume: 2023-11-23

Abstract: The mRNA transcript of the human STMN2 gene, encoding for stathmin-2 protein (also called SCG10), is profoundly impacted by TAR DNA-binding protein 43 (TDP-43) loss of function. The latter is a hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Using a combination of approaches, including transient antisense oligonucleotide-mediated suppression, sustained shRNA-induced depletion in aging mice, and germline deletion, we show that stathmin-2 has an important role in the establishment and maintenance of neurofilament-dependent axoplasmic organization that is critical for preserving the caliber and conduction velocity of myelinated large-diameter axons. Persistent stathmin-2 loss in adult mice results in pathologies found in ALS, including reduced interneurofilament spacing, axonal caliber collapse that drives tearing within outer myelin layers, diminished conduction velocity, progressive motor and sensory deficits, and muscle denervation. These findings reinforce restoration of stathmin-2 as an attractive therapeutic approach for ALS and other TDP-43-dependent neurodegenerative diseases.

DOI: 10.1038/s41593-023-01496-0

Source: https://www.nature.com/articles/s41593-023-01496-0

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex