S**K
发帖数: 3648 | 1 i think so...too much beta amyloid plaques |
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G*********o
发帖数: 49669 | 2 专业，深邃，一针见血，入木三分
i think so...too much beta amyloid plaques |
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a*******e
发帖数: 428 | 3 怎么感觉最近记忆力下降的厉害。中学的时候，历史书上一页的话，基本上一节课下课
时就一字不差的背下来了。现在连个密码都经常忘。beta amyloid真的是从40开始就在
人脑袋里生长了么？ |
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s***a
发帖数: 384 | 4 J Neuropathol Exp Neurol. 2005 Sep;64(9):743-53.
Dynamic complexity of the microglial activation response in transgenic models
of amyloid deposition:
implications for Alzheimer therapeutics.
Morgan D, Gordon MN, Tan J, Wilcock D, Rojiani AM.
plz send to q*[email protected] |
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h***l
发帖数: 168 | 5 基础医学院院长应聘者学术报告
地点：逸夫楼507会议室
4月7日：
18:30-20:00 肖志诚 TAGging the Physiological Functions of APP in
Neurogenesis
20:00-21:30 庄正平 From Bed to Bench Research: Tissue Proteomics in
the Study of Disease Pathogenesis and Identification of Therapeutic Targets
4月8日：
08:30-10:00 王登顺 beta-amyloid degradation and Alzheimer's disease
10:00-11:30 尹玉新 PTEN is a new guardian of the genome |
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h********r
发帖数: 519 | 6 Signal enhancement of surface plasmon resonance based immunosensor using
gold nanoparticle-antibody complex for beta-amyloid (1-40) detection.
Lee JH, Kang DY, Lee T, Kim SU, Oh BK, Choil JW.
J Nanosci Nanotechnol. 2009 Dec;9(12):7155-60. |
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p****s
发帖数: 3153 | 7 Frankly speaking, AD is not caused by the overexpression of Abeta, because
Abeta is the product of amyloid precursor protein processed by beta- and
gamma-secretase. Mutations of APP itself or gamma-secretase can cause
increased concentration of Abeta, causing the disease. Of course if you have
duplicate copy of APP gene, you can get the disease easier than normal.
They are the main reasons of familial AD
I do know one protein, alpha-synuclein: The overexpression of this protein
can cause Parkins |
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s******y
发帖数: 28562 | 8 我觉得Alzheimer's disease 不可能是由单一因素引起的，
最可能的情况就是细胞内部的变性蛋白积累多了，然后负责清理变性蛋白的
系统（这个包括内噬泡和转运这些泡泡的细胞骨架系统）由于某些原因效率
跟不上来，所以变性的东西越来越多，导致细胞产生apoptosis 应答所以该
神经细胞就死掉了。
所以，我认为细胞骨架运输系统和变性蛋白清理系统是两个应该主要考虑的
因素。
那个amyloid 的假说存在很严重的原理上的问题，而且相关的研究根本
就还没有做彻底。不知道为什么Eli Lilly 要抱着侥幸心理花那么多钱去做
相关的药。
First
side
INSDIE |
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w**r
发帖数: 134 | 9 我不知道AD如此多其他的进展，我是受合成化学训练，AD也不是我的研究，我也只是跟
着主流的思路在走，对于你说的其他方面的考虑，我觉得主要是药物研发缺乏对应的研
究靶点，否则制药公司早就蜂拥而上了。药物研发特点是不一定背后的机制都很清楚，
黑箱情况下也能出药，等一切清楚了，早就没有蛋糕给你分了，这也就说明药物研究偏
应用研发，对基础的东西其实并不关心。
当然基础研究很重要，我想药物研发切入的时机也就很重要。
对AD再说两句，在ab amyloid假说出来前，Ache不足的假说下，发现ache inbibitor的
AD的药都上市的三个，疗效可想而知，对药厂来说，在已有的只是情况下能推出FDA满
意的药赚钱足够了。
希望大家对药物研发能有点新的认识
First
side
INSDIE |
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s******y
发帖数: 28562 | 10 关键就是amyloid body 作为疾病模型本身就是一个错误逻辑。
很多情况下面，药厂的确不关心具体的机理，而是关心如何筛选出一个
具体的分子，有疗效而且副作用小。但是如果测试某分子的疗效的模型根本
就是错的话，选出来的药不错才怪。
我觉得药厂们在目前学术界对Alzheheimer's disease的pathological reason
根本还没有定论的时候根本就不应该跟进。
药厂应该把精力和钱放在那些pathological reason 或者pathogen明确的病
上面，比方说各种传染病啊，HIV啊什么的。这些东西比较容易筛选出明确
的抑制分子。 |
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y***i
发帖数: 11639 | 11 amyloid和AD的相关性的联系的数据非常强。说是致病原因，我认为还是很可信的。
但r-secretase对Notch pathway非常重要，对这个酶动手是非常冒险的事情。不过现
在的药连抑制转录表达的都有，都是毒得不能再毒。
，相 |
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y***i
发帖数: 11639 | 12 有啊，这是最早做的实验之一。诱导后老鼠过些天就变傻了。神经细胞被破坏，有纤
维性的amyloid大量积累。不过乱七八糟的蛋白过表达，老鼠估计总有很大的机会都很
难承受。所以这个是支持性的，但不是决定性的证据。
异直
个因 |
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h*******o
发帖数: 4884 | 13 First of all, more and more people in the field realize that familial AD and
sporadic AD might well be two different diseases.
In sporadic AD, Amyloid is not best correlated with disease, instead Tau
pathology correlates better. However,that's not saying that tau is the cause
of the disease.
Targeting BACE or gamma-secretase was wrong from the begining, considering
the side effect of gamma-secretase and the complication of Notch signalling
pathway.
I think a lot of people already predicted the f |
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h*******o
发帖数: 4884 | 14 BACE was not found to be hyper-active or over-express in either FAD or SAD...
My point is that target at Amyloid generation could be wrong from the
begining. |
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h*******o
发帖数: 4884 | 15 Most of the vaccine candidate worked beautifully in animal models, which are
transgenic models (in a sense more similar to FAD). None of them worked in
human trials so far. They did reduce amyloid load or plaques (thanks to PIBS
compound and PET image), but no improvement in cognitive function. |
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A******y
发帖数: 2041 | 16 I thought most amyloid forming transgenic mice don't have AD. |
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w****k
发帖数: 6244 | 17 it's a good hypothesis, and it can explain why amyloid plaque is not well
correlated to the pathology.
Since the oligomer is toxic, deposition as plaque is relatively protective. |
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z**a
发帖数: 243 | 18 能帮忙找下这篇文章全文么？谢谢！
J Alzheimers Dis. 2010 Apr;20(1):145-57. Overexpression of tau proteins
antagonizes amyloid-beta-potentiated apoptosis through mitochondria-
caspase-3 pathway in N2a cells. Wang ZF, Yin J, Zhang Y, Zhu LQ, Tian Q,
Wang XC, Li HL, Wang JZ. |
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h*******o
发帖数: 4884 | 19 Tau hyperphosphorylation is generally considered as downstream to Amyloid.
secretase |
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d******1
发帖数: 709 | 21 别把疯牛病和其他病相提并论，至今疯牛病的传染机制还不清楚。Amyloid是病因还是
附带的症状都不清楚。况且又不能通过空气传播。再说你也太小看免疫系统了，有空多
研究一下单克隆抗体药物。那个抗老年痴呆的抗体，可惜最后没通过临床。 |
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h********r
发帖数: 519 | 22 97-99 publications. NIU
Xianxin Hua, Zachary Miller, Geng Wu, Yigong Shi, Harvey F. Lodish (1999).
Specificity in TGF-beta-induced Transcription: Interactions of Promoter DNA,
Smad3 and TFE3. Proc. Natl. Acad. Sci. 96, 13130-13135.
Jie-Oh Lee, Haijuan Yang, Maria-Magdalena, Antonio Di Cristofano, Tomohiko
Maehama, Yigong Shi, Jack E. Dixon, Pier P. Pandolfi, and Nikola P.
Pavletich (1999). Crystal Structure of the PTEN Tumor Suppressor:
Implications for Its Phosphoinositide Phosphatase Activity ... 阅读全帖 |
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J**a
发帖数: 215 | 23 她是牛的不行哦。楼主看网名好像是physics的。以前MIT一个AP，Matthew Lang就和她
合作研究Prion amyloid fiber的mechanical properties.不过Matthew木有拿到tenure
去了Vanderbilt... |
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c********r
发帖数: 189 | 24 做neurodegeneration的应该评一下这篇“ApoE-Directed Therapeutics Rapidly
Clear β-Amyloid and Reverse Deficits in AD Mouse Models ”
是不是很promising？ |
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d******1
发帖数: 709 | 25 Freeze–Thaw Cycle is a way to make protein amyloid. |
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d******1
发帖数: 709 | 26 A more recent, biophysical definition is broader, including any polypeptide
which polymerizes to form a cross-beta structure, in vivo, or in vitro. Some
of these, although demonstrably cross-beta sheet, do not show some classic
histopathological characteristics such as the Congo red birefringence.
http://en.wikipedia.org/wiki/Amyloid |
|
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b******y
发帖数: 627 | 28 roughly remember there was a science paper for designing highly stable
proteins by optimizing packing in the core. They were able to make a small
protein very stable. just don't remember which paper. if i recall, I will
let you know.
Make sure not to use ww domains (although they are small enough) because
they are all marginally stable and may form amyloid fiber if multiple ones
are used in a row. |
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b******y
发帖数: 627 | 29 roughly remember there was a science paper for designing highly stable
proteins by optimizing packing in the core. They were able to make a small
protein very stable. just don't remember which paper. if i recall, I will
let you know.
Make sure not to use ww domains (although they are small enough) because
they are all marginally stable and may form amyloid fiber if multiple ones
are used in a row. |
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c********g
发帖数: 1106 | 30 顶。提出 amyloid cascade hypothesis (现在Alzheimer's disease 成因的最主要
假说之一)的 Science 小文章也才两页。 |
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p****s
发帖数: 3153 | 31 楼主是不是想干在amyloid领域干倒dobson这样的事情？省省吧，那个领域就是他开发
的。万一我说中了楼主别着急，我对你的文章也没有兴趣 |
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m*******m
发帖数: 442 | 32 随便拎出个alzheimer， 研究了这么多年， 还是停留在amyloid beta 上。结果各种扑
上去的公司的compound， blocking antibodies都没有效。
进展 |
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b******y
发帖数: 627 | 33 My guess is that A protein is probably multivalent, i.e. one A protein can
bind more than on B. Even if one A can only bind one B, GST is a dimer and a
GST-A dimer can bind two B and increase the local concentration of B.
Furthermore, Glutathione bead substantiates the local concentration effect
by binding more than one GST-A dimer in the vicinity of each other. As such,
the self-assembly activity of B is greatly increased and the whole system
including all beads, all GST-A and all B forms a sin... 阅读全帖 |
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l********n
发帖数: 260 | 34 Absence of A673T amyloid-β precursor protein variant in Alzheimer's disease
and other neurological diseases
please send to j***********[email protected]
Thx a lot |
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a****i
发帖数: 21 | 35 这期的Science针对2012年“ApoE-Directed Therapeutics Rapidly Clear β-Amyloid
and Reverse Deficits in AD Mouse Models” 这篇文章发了四篇Comments，对12年
的文章的结果进行质疑，每篇文章的署名集合了AD领域各个山头的力量，蔚为壮观，令
人叹为观止。 |
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A******y
发帖数: 2041 | 36 That's because what's working in AD is the thing that ApoE is carrying not
the ApoE itself. You can quote me on it when someone discovers a semi-good
therapeutic and it won't be anything related to the beta-Amyloid. |
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l***d
发帖数: 1798 | 37 大哥，赶紧读读
哪里提到
“很多ad病人其实是吃疯牛得病的”
我一看这个abstract是在说（文科生，你好好读读文章啊）
Prion diseases are widely recognized for their transmissibility, and it is t
his feature that has been studied most extensively. In recent years, public
health concerns over the transmission of animal forms of prion disease, such
as bovine spongiform encephalopathy and chronic wasting disease, to humans
has only augmented the notion that prion diseases are primarily infectious.
Yet within the spectrum of human prion diseases, often ov... 阅读全帖 |
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l***d
发帖数: 1798 | 38 我给你总结一下这个文章的大意，
文科生
这个文章是说prion 和ad有些共性
1.虽然这两个病设计不同的蛋白和多肽，但是都能misfold and aggregate成结构相似的
amyloid fibrils with cross-beta structures.
2. 同时misfold的过程，经常参与一些cu的结合（其实不仅仅是cu, zn, ca在不同neur
odegenerative dieseases都会参与）
文科生，露怯了
这篇文章，有个毛证据是说
“很多ad病人是吃疯牛得病的” |
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h*******o
发帖数: 4884 | 39 ......
您不但逻辑不行，英语也不行，而且还没有背景知识
给您简单介绍一下吧：
prion disease 的特性是可以transmissible
现在有某些研究表明tau pathology也会出现inter neuron／synapse transmission，
而amyloid beta也可以自身aggregate， 这种方式也和prion有类似的地方，
所以， 从这个意义上有人认为AD也有可能是一种transmissble disease，但是AD和Prp
根本就是2个不同的疾病
你倒好，直接变成AD是吃疯牛造成的
你这个逻辑就好比 我说因为你have sex的方式和猪类似，所以你是猪一个道理 |
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d****d
发帖数: 214 | 40 Niklas Pollard
Reuters
8:24 a.m. CDT, October 7, 2013
STOCKHOLM (Reuters) - Three U.S.-based scientists won the 2013 Nobel
medicine prize on Monday for their work on how hormones and enzymes are
transported within and outside cells, giving insight into diseases such as
diabetes and Alzheimer's.
Americans James Rothman, 62, Randy Schekman, 64, and German-born Thomas
Suedhof, 57, separately mapped out one of the body's critical networks that
uses tiny bubbles known as vesicles to ferry chemicals s... 阅读全帖 |
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T****i
发帖数: 15191 | 42 以前听他讲过这个。当时就觉得那也太牛了吧？简直神奇啊。从那以后就不敢相信他实
验室出来的东西了。现在再次印证了，很多大牛的牛，是吹牛的牛。最近这么多大牛明
目张胆忽悠甚至系列作假，事发之后找个千老替罪，自己仍然做大牛。只能说这个体系
病的不轻。
Amyloid |
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r***l
发帖数: 163 | 43 【 以下文字转载自 MedicalDevice 讨论区 】
发信人: resol (丝路), 信区: MedicalDevice
标 题: 有没有熟悉体外诊断试剂盒的朋友？
发信站: BBS 未名空间站 (Sat Nov 15 20:53:55 2014, 美东)
有国内朋友想做进口体外诊断试剂盒，特别对下列免疫比浊项目有兴趣。不知道版上有
没有做这块可以合作的朋友？或许能指点下去哪里找这样的合作伙伴比较靠谱，不胜感
激！
如果供应商在中国没有代理，可以帮他们在中国跑审批做代理。如果已经有代理，是不
是还能帮他们在不同地区销售或者代理？还请有经验的高手指点一二。另外，请教下怎
么查这些试剂盒的价格，多谢！
免疫比浊项目
1． PGⅠ 胃蛋白酶原Ⅰ
2． PGⅡ 胃蛋白酶原Ⅱ
3． HP 胃幽门螺旋杆菌
4． RbP 视黄醇结合蛋白
5． NGAL 人类中性粒细胞明胶酶相关载脂蛋白
6． CystatinC 胱氨酸蛋白酶抑制剂 C
7． Myo... 阅读全帖 |
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i*****i
发帖数: 154 | 44 This article has been retracted at the request of the authors. Donmez et al.
(2010) reported that SIRT1 suppressed Alzheimer’s disease in a mouse model
by upregulating the ADAM 10 α-secretase gene via coactivation of the
retinoic acid receptor, RARβ. Increased α-secretase bypassed the
processing of APP by the β-secretase, thereby reducing the amyloid burden.
It has come to our attention that several figures in the paper contain
images in which gel lanes were spliced together without appropriate
... 阅读全帖 |
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w*********o
发帖数: 3030 | 45 Don't get too excited. I predict that using omics for cancer treatment is
the next biggest bust after the amyloid-beta :) |
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b****r
发帖数: 17995 | 46 amyloid-beta 有什么bust吗，没有感觉到过，不就是发现了一种常见病的机理，没觉
得有多少后续投资进去，跟omics是没法比的 |
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w*********o
发帖数: 3030 | 47 Don't get too excited. I predict that using omics for cancer treatment is
the next biggest bust after the amyloid-beta :) |
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b****r
发帖数: 17995 | 48 amyloid-beta 有什么bust吗，没有感觉到过，不就是发现了一种常见病的机理，没觉
得有多少后续投资进去，跟omics是没法比的 |
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h*******o
发帖数: 4884 | 49 做AD的， 到目前为止 target abeta的尝试没有一个成功的 （不管是直接的abeta
vaccine， abeta 抗体， 还是beta secretase inhibitor， gamma secretase
inhibitor），包括前段时间（三月份）炒的沸沸扬扬的biogen的phase 1的 drug， 结
果到了7月份出来的新的trial data就股价暴跌了
gamma secretase inhibit的目前的最大问题是notch pathway的off target effect，
当然提高了gamma secretase的结构可能对于解决这个off target 问题有帮助，但是最
基本的问题还是， 减少了abeta 到底对于AD有没有clinical benefit
个人的感觉是现在industry 已经锁死在abeta这个target上面了，因为投入太多， 输
不起， 硬着头皮也要上
AD病人没效果的，就往MCI推， MCI效果还不明显，就要把therapeutic window更加提
前。
但是最大的问题是abeta hypothesis可能从一开始就... 阅读全帖 |
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a****i
发帖数: 21 | 50 今天看文献时才注意到。比如这篇文献Central role for PICALM in amyloid-β
blood-brain barrier transcytosis and clearance Nature Neuroscience 18, 978
–987 (2015) doi:10.1038/nn.4025 Received 10 March 2015 Accepted 21 April
2015 Published online 25 May 2015
每个统计图的原始数据都放在一个EXCEL表格里。这是杂志要求，还是作者严谨。。。
第一次注意到，好奇 |
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