來自美生物制藥公司Biogen Idec Inc、中國香港大學(xué)解剖學(xué)系和腦與認知科學(xué)國家重點實驗室（State Key Laboratory of Brain and Cognitive Sciences）等單位的研究人員發(fā)現(xiàn)了一種治療中樞神經(jīng)系統(tǒng)CNS脫髓鞘疾?。╠emyelinating diseases）的新方法,。這一研究成果公布在《自然—醫(yī)學(xué)》雜志上。
領(lǐng)導(dǎo)這一研究的是香港大學(xué)醫(yī)學(xué)院解剖學(xué)系副教授,，中山大學(xué)客座教授的吳武田教授,，其一直致力于神經(jīng)損傷和再生機制方面的基礎(chǔ)研究。
脫髓鞘疾?。╠emyelinating diseases）,，譬如多發(fā)性硬化癥（multiple sclerosis，MS,，一種自體免疫性疾病(autoimmune disease),，即患者體內(nèi)的免疫系統(tǒng)無法分辨何者是自己的細胞，何者為外來侵犯物,，造成免疫系統(tǒng)攻擊自身的組織）的一個重要特征就是神經(jīng)細胞周圍髓鞘（myelin sheath）丟失,，這主要是因為中樞神經(jīng)系統(tǒng)（central nervous system，CNS）中發(fā)生了炎癥反應(yīng)和膠質(zhì)增生（gliosis）,。
因此目前的治療主要是靶向抗炎機制,，達到阻礙或延緩疾病擴散的目的，而針對軸突髓鞘質(zhì)（myelin）的一種方法則提供了抑制以及可能逆轉(zhuǎn)疾病擴散的新治療方法,，之前的研究發(fā)現(xiàn),，含亮氨酸重復(fù)序列和免疫球蛋白結(jié)構(gòu)域的Nogo受體作用蛋白（LINGO-1）是一種體內(nèi)體外少突膠質(zhì)細胞（Oligodendrocyte）分化和髓鞘（myelination）的負調(diào)控因子。
在這篇文章中,，研究人員利用LINGO-1基因敲除或者抗LINGO-1功能的抗體造成LINGO-1功能缺失,，結(jié)果發(fā)現(xiàn)這種缺陷型中實驗性自身免疫性腦脊髓炎（experimental autoimmune encephalomyelitis）功能復(fù)原，這通過生物性軸突完整性增加——彌散張量磁共振成像（magnetic resonance diffusion tensor imaging）和髓鞘新形成——電子顯微（electron microscopy）獲得確認,。從而研究人員提出針對LINGO-1或其途徑的對抗治療是一種治療中樞神經(jīng)系統(tǒng)CNS脫髓鞘疾病的新方法,。
原始出處:
Nature Medicine 13, 1228 - 1233 (2007)
Published online: 30 September 2007 | doi:10.1038/nm1664
LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis
Sha Mi1,7, Bing Hu2,7,8, Kyungmin Hahm1, Yi Luo1, Edward Sai Kam Hui6, Qiuju Yuan2, Wai Man Wong2, Li Wang2, Huanxing Su2, Tak-Ho Chu2, Jiasong Guo2, Wenming Zhang2, Kwok-Fai So2,3,4, Blake Pepinsky1, Zhaohui Shao1, Christilyn Graff1, Ellen Garber1, Vincent Jung1, Ed Xuekui Wu6 & Wutian Wu2,3,5,7
Demyelinating diseases, such as multiple sclerosis, are characterized by the loss of the myelin sheath around neurons, owing to inflammation and gliosis in the central nervous system (CNS). Current treatments therefore target anti-inflammatory mechanisms to impede or slow disease progression. The identification of a means to enhance axon myelination would present new therapeutic approaches to inhibit and possibly reverse disease progression. Previously, LRR and Ig domain–containing, Nogo receptor–interacting protein (LINGO-1) has been identified as an in vitro and in vivo negative regulator of oligodendrocyte differentiation and myelination. Here we show that loss of LINGO-1 function by Lingo1 gene knockout or by treatment with an antibody antagonist of LINGO-1 function leads to functional recovery from experimental autoimmune encephalomyelitis. This is reflected biologically by improved axonal integrity, as confirmed by magnetic resonance diffusion tensor imaging, and by newly formed myelin sheaths, as determined by electron microscopy. Antagonism of LINGO-1 or its pathway is therefore a promising approach for the treatment of demyelinating diseases of the CNS.
Biogen Idec Inc., 14 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Research Center of Reproduction, Development and Growth, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Department of Electrical and Electronic Engineering, Faculty of Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
These authors contributed equally to this manuscript.
Present address: School of Life Science, The University of Science and Technology of China, Hefei, Anhui 230027, China.
Correspondence to: Wutian Wu2,3,5,7 e-mail: [email protected]
Correspondence to: Sha Mi1,7 e-mail: [email protected]
