多發(fā)性硬化癥是一種影響患者神經(jīng)系統(tǒng)的自體免疫疾病，導致患者身體和認知功能的喪失,。如今,，研究人員鑒別出一種可能是影響進展性多發(fā)性硬化癥的因子，新成果發(fā)表在8月在線出版的《自然—免疫學》期刊上,。
多發(fā)性硬化癥有不同類型的疾病進展模式,。臨床上，依病程進展可分為四類：復發(fā)—緩解型,、次發(fā)—漸進型,、首發(fā)—漸進型和漸進—復發(fā)型,。其疾病的進展又可簡單分為兩個階段，復發(fā)—緩解型階段主要為免疫引起的發(fā)炎反應,，而漸進階段則包含了神經(jīng)的退化,。
但在復發(fā)—緩解型階段后，病情會出現(xiàn)不可逆轉(zhuǎn)的進展型發(fā)展,。目前還沒有針對這種進展型多發(fā)性硬化癥的有效療法,。
Howard Weiner和Francisco Quintana領(lǐng)導的一個研究小組鑒別出一種名為15-HC的脂肪，這種脂肪在進展型患者體內(nèi)的含量提高了,，而在復發(fā)—緩解型患者體內(nèi)卻沒有這種情況,。科學家們發(fā)現(xiàn),，15-HC激活了一種名為PARP-1的受體,，阻止了PARP-1的活性，降低了進展型多發(fā)性硬化癥模式小鼠的病程,。
進一步的研究還將確認一個新問題：控制PARP-1的活性是否治療進展型多發(fā)性硬化癥的潛在方法,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Immunology 16 August 2009 | doi:10.1038/ni.1775
Toll-like receptor 2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinflammation in progressive EAE
Mauricio F Farez1,4, Francisco J Quintana1,4, Roopali Gandhi1, Guillermo Izquierdo2,3, Miguel Lucas2 & Howard L Weiner1
Abstract
Multiple sclerosis is an inflammatory disease of the central nervous system that begins as a relapsing-remitting disease (RRMS) and is followed by a progressive phase (SPMS). The progressive phase causes the greatest disability and has no effective therapy, but the processes that drive SPMS are mostly unknown. Here we found higher serum concentrations of 15-hydroxicholestene (15-HC) in patients with SPMS and in mice with secondary progressive experimental autoimmune encephalomyelitis (EAE) but not in patients with RRMS. In mice, 15-HC activated microglia, macrophages and astrocytes through a pathway involving Toll-like receptor 2 (TLR2) and poly(ADP-ribose) polymerase 1 (PARP-1). PARP-1 activity was higher in monocytes of patients with SPMS, and PARP-1 inhibition suppressed the progression of EAE. Thus, the TLR2–PARP-1 pathway is a potential new therapeutic target in SPMS.
1 Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
2 Molecular Biology Service, University of Sevilla, Sevilla, Spain.
3 Multiple Sclerosis Unit, University of Sevilla, Sevilla, Spain.
4 These authors contributed equally to this work.
