干细胞之家 - 中国干细胞行业门户第一站

 

 

搜索
朗日生物

干细胞技术讨论区

干细胞文献资源库

干细胞临床应用技术交流

免疫细胞治疗专区

欢迎关注干细胞微信公众号

查看: 63762|回复: 146
go

An unlikely culprit in prion diseases

Rank: 7Rank: 7Rank: 7

积分
威望
0  
包包
3465  
发表于 2009-3-6 00:11 |显示全部帖子
Lindquist/AAAS
7 n! d  @. m& V" c+ X
8 D' F4 `8 E* j3 l2 S* @  W1 d% BForget the obvious. The toxicity of the prion protein (PrP) may have nothing to do with its most highly visible version: the infectious, detergent-resistant, plaque-forming fibrillar PrPSc seen in diseased brains of scrapie-infected sheep and mad cows. Instead, Jiyan Ma, Robert Wollmann (University of Chicago, Chicago, IL), and Susan Lindquist (MIT, Cambridge, MA) point the finger at cytosolic PrP.
& y. D# a& c$ g/ F& R
# D/ M1 d) r/ I/ ]8 j, y3 uMinor misfolding events probably lead to continual ejection of PrP from the ER into the cytosol for degradation by proteasomes. The team's inhibition of cytosolic proteasomes preferentially killed cells expressing PrP, and expression of PrP lacking ER translocation signals was highly toxic to neural cells both in vitro and in vivo. Transgenic mice producing cytosolic PrP suffered from unsteady gait and massive neuronal loss due to degeneration rather than problems in development. Thus, a cytosolic PrP rather than extracellular PrPSc aggregate appears to be the toxic species.
! [$ ?9 R2 L( N/ a& p3 @
+ Q  c' [. x  t8 I"This represents a real breakthrough in the prion field," says Peter Lansbury (Harvard Medical School, Boston, MA). At the same time, he says, "I'm not at all surprised. It's very consistent with all the other neurodegenerative diseases."
* [0 N' ?5 z6 t' i. T3 F# J4 ]+ T' l5 L6 M* [2 N
Fibrillar forms of ?-amyloid (in Alzheimer's disease) and -synuclein (in Parkinson's disease) initially dominated theories of pathogenesis in these neurodegenerative conditions. But others have demonstrated extraordinary toxicity of microinjected ?-amyloid protein, and Lansbury has pointed to cytoplasmic protofilaments—a non-plaque form that resemble pore-forming bacterial toxins—as the toxic species.
* [/ \8 h& i/ u$ i& A( c7 n# Y5 ]8 Q
The prion field, however, has assumed that the infectious aggregates of PrPSc are also the toxic form. "The whole field has been driven by neuropathology," says Lansbury. "That's why it's so good to have people from different backgrounds working on this.  isn't subject to the years and years of focus on amyloid plaques."9 M  p& E0 \- T( `7 W
9 l/ k4 E( R3 k# }* H5 I
The Lindquist team also showed that proteasome inhibition could eventually lead to formation of PrPSc. Lindquist suggests that the toxicity of cytosolic PrP may be a way of sabotaging this event. In this theory, if folding problems lead to excessive ejection of PrP from the ER to the cytosol, the cell commits suicide rather than risk making the infectious version, PrPSc. Cytosolic PrP, says Lindquist, "is so extremely toxic that it may represent a defense mechanism."
8 O  h0 t6 i: Q
" f; b! h$ y) w8 a; J3 iReferences:
. X8 F* K" w; n. a! @! q2 Y+ _5 X
; ?1 B4 y( ^( }8 ?9 y% V' S% mMa, J., et al. 2002. Science. 10.1126/science.1073725.
  ?' n, L$ s9 [* w6 l# K5 ^/ t( O% l
Ma, J., and S. Lindquist. 2002. Science. 10.1126/science.1073619.(Soluble prion protein makes mice unstead)

Rank: 2

积分
77 
威望
77  
包包
1964  
发表于 2015-5-23 17:02 |显示全部帖子
是楼主原创吗  

Rank: 2

积分
73 
威望
73  
包包
1833  
发表于 2015-6-7 14:35 |显示全部帖子
今天没事来逛逛  

Rank: 2

积分
75 
威望
75  
包包
2193  
发表于 2015-6-11 15:54 |显示全部帖子
干细胞之家微信公众号
羊水干细胞

Rank: 2

积分
89 
威望
89  
包包
1794  
发表于 2015-6-20 14:17 |显示全部帖子
说的不错  

Rank: 2

积分
107 
威望
107  
包包
1889  
发表于 2015-6-28 14:18 |显示全部帖子
这样的贴子,不顶说不过去啊  

Rank: 2

积分
101 
威望
101  
包包
1951  
发表于 2015-7-21 21:35 |显示全部帖子
晕死也不多加点分  

Rank: 2

积分
107 
威望
107  
包包
1889  
发表于 2015-7-30 17:01 |显示全部帖子
回复一下  

Rank: 2

积分
72 
威望
72  
包包
1859  
发表于 2015-9-13 15:54 |显示全部帖子
内皮祖细胞

Rank: 2

积分
77 
威望
77  
包包
1730  
发表于 2015-9-15 10:54 |显示全部帖子
一个子 没看懂  
你需要登录后才可以回帖 登录 | 注册
验证问答 换一个

Archiver|干细胞之家 ( 吉ICP备13001605号 )

GMT+8, 2020-8-9 08:04

Powered by Discuz! X1.5

© 2001-2010 Comsenz Inc.