篇名:
綜說:從分子生物學觀點探討傳染性海綿狀腦病致病機轉Review:Pathogenesis of Transmissible Spongiform Encephalopathies in Molecular Biology Aspects
作者:
李淑慧、張國慧、鍾明華、林士鈺
中文摘要:
傳染性海綿狀腦病(transmissible spongiform encephalopathies; TSEs) ,因其會造成人類或動物腦組織海綿狀病變而被命名。1982年美國神經生化學家Prusiner S.B 於科學(Science)雜誌發表羊搔癢症 (scrapie) 之致病物質為一不含核酸,僅具蛋白質之粒子,並將其命名為proteinaceous infection particle,此具感染力之病因簡稱prion。正常動物及人類許多細胞表面皆含有prion,簡稱PrPC,c 代表細胞 (cellular);此PrPC正常結構為四個 a 螺旋結構,由於不明原因使其中兩個 a 螺旋結構異構 (conformation) 為 b 褶板樣結構,發生異構現象之prion稱PrPSc,Sc代表scrapie,以下簡稱PrPSc,具感染力與病原性。PrPSc 無法被正常蛋白酵素所水解,故會堆疊於腦組織中,尤其是神經細胞,引起神經細胞凋零 (apoptosis),繼而星狀細胞移除凋零死亡之神經細胞,形成腦組織之空洞變化。綜合近年來相關文獻可得知人類或動物感染PrPSc,大致可分為兩種路徑,一為經口感染受污染之食物,將PrPSc經口食入,在扁桃腺增殖,經由免疫系統,主要是B細胞,將PrPSc帶入周邊淋巴結與脾臟,follicular dendritic cells會幫助PrPSc 之複製,再經由B細胞將PrPSc 帶入周圍神經,最後感染腦神經細胞;另一感染途徑為醫源性感染 ( iatrogenic ), 經注射荷爾蒙、輸血、外科手術等醫療行為而感染PrPSc,此具病原性prion可經由血液或淋巴液感染周圍神經,最後感染腦神經細胞,造成海綿狀腦病。
英文摘要:
SUMMARY Transmissible spongiform encephalopathies (TSEs) are often propagated by extracerebral inoculation. The mechanism of spread from peripheral portals of entry to the central nervous system (neuroinvasion) is complex. While lymphatic organs show early accumulation of prions, B-cells and follicular dendritic cells are required for efficient neuroinvasion. Intact prions enter the central nervous system probably via peripheral nerves and may need a cellular counterpart of prion protein (PrPC) for propagation. TSEs are characterized by accumulating an abnormal isoform (PrPSc) of the host-encoded PrPC in brain. In 1982, Prusiner firstly purified the infectious agent from hamster brain and introduced the term “prion” for proteinaceous infectious particle. The PrP isoforms contain identical amino-acid sequence, yet differ in their overall secondary structure with the PrPSc isoform, possess a higher β-sheet and lower α-helix content than PrPC. In 1967, Griffith suggested that the possible cause of scrapie may be a self-replicating protein. Consequently, by a series of experiments, Prusiner et al. demonstrated that the infectivity was increased when a specific protein was contained in the sample. In the other words, the infectivity correlated closely with the concentration of the protein. According to these results, Prusiner proposed and developed the “protein-only” hypothesis. Weissmann et al. cloned and sequenced the host PrP gene, which encodes for PrPC. By unknown mechanisms, an autocatalytic cycle was probably initiated by introducing exogenous PrPSc, and resulted in the conversion of a-helix intoβ-sheet conformation. Unlike the a-helical PrPC, the protease-resistant core of PrPSc is predominantly b-sheet and possesses a tendency to polymerize into amyloid fibrils. Nevertheless, the molecular mechanism of the conformation rearrangement of PrPC into PrPSc is still unknown.
備註:
年份:西元 2001 年
期別:第 37 期
詳細內容:
1996年英國政府發表狂牛症,又稱牛海綿狀腦病 (bovine spongiform encephalopathy,簡稱BSE),疑與新型變種庫賈氏病 (variant Creutzfeldt-Jakob disease,簡稱vCJD) 有關之訊息後 (1996, BSE inquiry),狂牛症及海綿狀腦病變是常被提到的話題[1,2,3]。海綿狀腦病的名詞並非是整個腦子變得像海綿般,其實患者的大腦外表看起來只是有點萎縮,主要是其大腦切片在顯微鏡下顯示神經細胞大量死亡,而存活的神經細胞之間有許多的空隙存在,因為沒被H & E染上色,看起來如同海綿的空洞一樣[2,6,8]。近年來BSE已掀起全世界之恐慌,本來英國BSE的疫情已獲得控制,但最近在法國、德國、西班牙、比利時等國卻陸續爆發數十件人、畜的病例,才驚覺BSE已悄悄地入侵歐洲,法國的「世界報」稱此事件為「歐洲危機」[3,20]。以往研究認為PrPSc只會在羊品系中傳播,然近年來隨著證實人類食入含PrPSc病原之牛肉而感染vCJD,陸續證實其他動物也會感染PrPSc,包括鹿、糜鹿、貂、貓、獅、豹等[7,17,18,19]。據研究顯示,BSE之所以會在歐洲死灰復燃,關鍵因素可能在於飼料問題,故歐盟已通過法令,自2001年起全面禁止使用含有動物製品的飼料供牛、豬及家禽食用,為期6個月,以避免畜齡30月以上的動物感染BSE進入食物鏈,造成危害。所幸臺灣迄今未有病例報告,但自英國BSE發病高峰期1990-1996年間,臺灣自英進口肉骨粉達四萬五千公噸,經調查這些肉骨粉僅用於禽類,使得臺灣發生BSE之風險大為降低,但為防範於未然,實有必要了解此病之致病機轉,緣此,收集數十篇文獻,嘗試從分子生物學之觀點探討其致病機轉,供防疫策略之研擬及從事本病監控及研究之基本參考資料。
附件下載:
附件名稱:
分子生物學觀點
行政院農業委員會家畜衛生試驗所版權所有
服務信箱:info@mail.nvri.gov.tw
Tel:0800-068112、02-26212111
FAX:02-2622-5345

免責聲明
 新北市淡水區中正路376號