z********1
发帖数: 997 | 1 Biogen Alzheimer’s drug
Human:
4/29/2015:
Clinical trials of the vaccine, which is
called Betabloc and made by Dublin-based Elan Pharmaceuticals, are already
under way in the UK.
Preliminary results appear to show it is safe and has no side-effects. About
80 patients with mild to moderate forms of Alzheimer's are taking part in a
second set of safety trials, which are close to completion.
On mice:
Dec 8 2014
Researchers at Standford University discovered that nerve cells die because
cells which ... 阅读全帖 |
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f*******3
发帖数: 122 | 2 RE: Applicant’s Name
To Whom It May Concern:
I am an Associate Professor in Biochemistry and Molecular Biology at the ___
___________________. My current research interests are ____________________
____________________________________________________________________________
____________________________________________________________________________
__________________. I am an author of over __________research publications
in the general field of __________________ , which have been cited ... 阅读全帖 |
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s******y
发帖数: 28562 | 3 我觉得拿这个当drug target在生物原理上就是错误的。
gamma-secretase 虽然直接负责amyloid的成熟/生成,
但是并不是导致amyloid 变性的原因。抑制了它的功能很难说和Alzheimer's
有什么直接的逻辑关系。
而且这个酶在正常细胞里就存在，说明它肯定是有正常生理功能的。
这么广泛的到处去抑制它，不产生不良后果才怪了。 |
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s******y
发帖数: 28562 | 4 上面已经有别的同学指出了，amyloid plaque 和AD的因果关系不明，
甚至有证据指出amyloid plaque可能是神经系统自我保护的一个response action. |
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y***i
发帖数: 11639 | 5 家族性的AD的变异一半以上是在r-secretae (Psn)上。而这个酶对amyloid plaque的
影响也非常清楚，所以这个酶和AD显然强烈相关，针对这个酶动手，就致病机理上是最
自然的事情，所以这不是个随便乱蒙的例子。现在没多少drug target比r-secretase更
清楚。也许你的总的论点是有道理的，但具体到这个r-secretae上，我想你举了错误的
例子。
唯一的问题是r-secretae是最重要的Notch pathway上必须酶之一。这个基因一旦彻
底敲除（把卵子mRNA也去掉），基本上什么都发育不出来，流产都免了。在果蝇胚胎发
育时大部分细胞都会变成神经细胞，是CPU级别的pathway。Notch pathway在成人中的
功能不完全清楚，但已经知道的部分也相当重要，比如免疫系统的维持。所以针对r-
secretae的毒性估计就从此而来。
amyloid
过。
plaque |
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p*****m
发帖数: 7030 | 6 你这第一点不说明什么吧 我也不觉得amyloid是bace hyperactive的结果 但是bace is
required for abeta generation也是真的对吧。
你说amyloid generation可能不是问题的关键这个也许是对的 但是有什么solid证据么
现在？
... |
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h*******o
发帖数: 4884 | 7 check other failed amyloid vaccine trials.
They all remove amyloid like a miracle, but did not improve cognitive function in
human trials, and some even failed in animal trials.
is |
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h*******o
发帖数: 4884 | 8 That's like schrodinger's cat, no way to solve that.
But in common sense, if amyloid is the cause, even if it is relatively late
stage of AD, direct removal of amyloid and plaque should exert moderate
benefits. |
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h*******o
发帖数: 4884 | 9 I think it is up-regulating/activating microglia to devour amyloid
aggregates or plaques, which of course works in AD mouse model. I highly
doubt this will work in human trials.
As a matter of fact, over activation of microglia is believed to cause
inflammatory response thateventually lead to neuronal loss.
In my opinion, it is very much like the amyloid vaccine story. Works
beautifully in mouse models, failed or will fail at human trial. |
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l***d
发帖数: 1798 | 10 大哥你去读读文章好吧
这个报道也还是讲很多neurodegenerative dieseases
虽然，sequences不同，涉及不同的病症，
但是都会misfold成结构相似的amyloid fibrils
而且越来越多的证据表明
其实amyloid fibrils并不是致毒的species
而是那些中间态的oligomers
我靠，给文科生科普真可怕。 |
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s******y
发帖数: 28562 | 11 SIRT1 Suppresses β-Amyloid Production by Activating the α-Secretase Gene
ADAM10
好看得一塌糊涂，就是里面指出的机理让人觉得too good to be true. 我几年前看了
一眼这个文章，眼珠子都快掉地上了。因为在我的理解中，sirtuin 应该是一个代谢途
径的调节者，所以有些间接的调节年老的功能。但是居然巧合到能够去调节β-Amyloid
，这个也未免太巧了。结果果然是too good and not true. |
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c********n
发帖数: 225 | 12 谈谈和蛋白打交道的日子 （八）
第八篇 轮回
引子
主题构思于美国独立日，一个国家的生日。每一个新事物的产生，往往都伴随着老事物
的离去。日月轮回， 周而复始。这在LIVE乐队一首经典的Lighting Crashes MTV里，
有着令人心动的视觉体现。旋律混合着实验室几个人深夜coffee break的aroma，深深
印在脑海：
oh now feel it comin' back again
like a rollin' thunder chasing the wind
forces pullin' from the center of the earth again
I can feel it.
这次来简单思考一下轮回吧。
最近施一公与Sjors Scheres合作得到了4.5A 分辨率γ secretase的晶体结构， 和
amyloid生成相关， 涉及到了蛋白在体内轮回的重要性，特别是在neurological
diseases的集中体现。
蛋白aggregation是一点一滴积累起来的，一旦形成就很难被细胞正常的protein
degradation机制消化掉。大量垃圾... 阅读全帖 |
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f********1
发帖数: 367 | 13 http://www.ncbi.nlm.nih.gov/pubmed/26493635
Brain. 2015 Oct 22. pii: awv313. [Epub ahead of print]
Passive immunotherapy targeting amyloid-β reduces cerebral amyloid
angiopathy and improves vascular reactivity.
Bales KR1, O'Neill SM2, Pozdnyakov N2, Pan F2, Caouette D2, Pi Y2, Wood KM2,
Volfson D2, Cirrito JR3, Han BH4, Johnson AW4, Zipfel GJ5, Samad TA1.
请将全文发送到[email protected]
/* */,并回复此贴.
谢谢! |
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x********i
发帖数: 905 | 14 2016 Breakthrough Prize in Life Sciences
The Breakthrough Prize in Life Sciences honors transformative advances
toward understanding living systems and extending human life, with one prize
dedicated to work that contributes to the understanding of Parkinson’s
disease and neurodegenerative disorders.
Edward S. Boyden, Massachusetts Institute of Technology: for the development
and implementation of optogenetics – the programming of neurons to express
light-activated ion channels and pumps, so that... 阅读全帖 |
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c********g
发帖数: 1106 | 15 dementia,血管源性的或者 amyloid引起的。差不多就是老年痴呆症。没什么有效的药。
你可以google dementia /alzheimer's disease /amyloid beta之类的研究研究。 |
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c********g
发帖数: 1106 | 16 dementia,血管源性的或者 amyloid引起的。差不多就是老年痴呆症。没什么有效的药。
你可以google dementia /alzheimer's disease /amyloid beta之类的研究研究。 |
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m****g
发帖数: 530 | 17 Data Suggest Pfizer's Humanized Anti-Amyloid Monoclonal Antibody was Well-
Tolerated in Patients with
Mild to Moderate Alzheimer's Disease
Safety Results from Dimebon in Combination with Donepezil Showed that
Combination was Well-Tolerated
NEW YORK--(BUSINESS WIRE)--Jul 15, 2009 - Pfizer Inc announced today results
from two Phase 1 safety
studies, one of PF-04360365, a humanized anti-amyloid monoclonal antibody (
mAb), and another of
dimebon (latrepirdine*) in combination with donepezil HCl tabl |
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d***a
发帖数: 13752 | 18 Fu并不在Department of Pharmacology吧。
看下面这个publication，1997年时，Fu所在的系叫Departments of Pathology,
Surgery, Physiology, and Medicine。这个系现在已经找不到了，应该是重组了。
这也可以解释Fu的简历中，毕业专业的变化。
http://www.pnas.org/content/94/10/5296.short
Amyloid-β peptide–Receptor for Advanced Glycation Endproduct interaction
elicits neuronal expression of macrophage-colony stimulating factor: A
proinflammatory pathway in Alzheimer disease
Shi Du Yan*,
Huaijie Zhu*,
Jin Fu*,
Shi Fang Yan*,
Alex Roher†,
... 阅读全帖 |
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k****z
发帖数: 1863 | 19 一群眼红的中国人傻逼：
http://www.pnas.org/content/94/10/5296.short
Amyloid-β peptide–Receptor for Advanced Glycation Endproduct interaction
elicits neuronal expression of macrophage-colony stimulating factor: A
proinflammatory pathway in Alzheimer disease
Shi Du Yan*,
Huaijie Zhu*,
Jin Fu*,
Shi Fang Yan*,
Alex Roher†,
Wallace W. Tourtellotte‡,
Tripathi Rajavashisth§,
Xi Chen*,
Gabriel C. Godman*,
David Stern*, and
Ann Marie Schmidt*
- Author Affiliations
*Departments of Pathology, Surger... 阅读全帖 |
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x******g
发帖数: 33885 | 20 Yan SD, Fu J., Soto C., Chen X., Zhu H., Al-Mohanna, F., Collison K., Zhu A.
, Stern E., Saido T., Tohyama, M., Ogawa, S., Roher, A and Stern, D. ERAB:
an intracellular protein that binds amyloid-ß peptide and mediates
neurotoxicity in Alzheimer’s disease. Nature 389:689-695, 1997. |
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x****6
发帖数: 4339 | 21 疯牛病 和 老年痴呆症的发病机制在 生物物理层面是一样的
就是蛋白质的异构折叠造成。
在老年痴呆症里，细胞的amyloid beta蛋白本来是一个一个分子以球体独立存在；但是
发病的细胞里，这个蛋白表达过高，导致蛋白的结构发生改变，许多分子聚集在一起，
形成一个巨大的蛋白复合物，最终把细胞撑破。
疯牛病也是类似，只不过这里的 关键蛋白是由一个病毒携带的蛋白导致的 |
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s*****r
发帖数: 11545 | 22 那不是有病毒么，怎么我听说就是蛋白导致结晶而且这种蛋白结晶本身可以独立传染。
如果不存在这病毒，生物体摄入该蛋白，尤其是通过消化道，怎么可能致病？ 更别扯
鸡巴蛋传染了。
: 疯牛病 和 老年痴呆症的发病机制在 生物物理层面是一样的
: 就是蛋白质的异构折叠造成。
: 在老年痴呆症里，细胞的amyloid beta蛋白本来是一个一个分子以球体独立存在
；但是
: 发病的细胞里，这个蛋白表达过高，导致蛋白的结构发生改变，许多分子聚集在
一起，
: 形成一个巨大的蛋白复合物，最终把细胞撑破。
: 疯牛病也是类似，只不过这里的 关键蛋白是由一个病毒携带的蛋白导致的
|
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x****6
发帖数: 4339 | 23 疯牛病病毒应该在被消化道消化以前就感染进入上皮细胞，进入通过血液了。
并且致病阮蛋白是很小的蛋白质，只有几十个氨基酸，算大分子里的小分子，可以到处
跑，甚至穿过血脑屏障
下图表示了 beta amyloid从单体重新折叠和聚集成超大分子纤维的过程 |
|
发帖数: 1 | 24 07 Nov 2019
Just as the clamor about Biogen’s seeking FDA approval for aducanumab with
one positive Phase 3 trial started to die down, a Chinese company garnered a
regulatory thumbs-up for its drug, also with one Phase 3 trial. On November
2, Shanghai Green Valley Pharmaceuticals announced that China’s National
Medical Product Administration (NMPA) had conditionally approved GV-971, aka
oligomannate, for the treatment of mild to moderate Alzheimer’s disease.
Full approval, expected to come in sp... 阅读全帖 |
|
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a***a
发帖数: 40617 | 26 second this
amyloid在外周神经里
跟alzheimer, parkinson成因类似 |
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g****d
发帖数: 3461 | 27
有道理
铝离子三个电，很难穿过细胞膜
必须用特殊离子通道或者泵才能吸收
现在还没听说铝通道。
蛋白质里沾上的金属离子＋2就顶天了，
三个正电要三个负的来稳定，复电氨基酸
太集中对蛋白质折叠非常不利
老年痴呆症脑细胞多发现Amyloid beta
集结沉淀，这个东西好像不用铝就可以出
折叠错误。 |
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d**********0
发帖数: 13081 | 28 这个学校是天才的摇篮， 300 中占了15名。。
The Harker School, San Jose, CA
Dixit, Shikhar, 17
Immunomodulation by Human Retinal Pigment Epithelial Cell Line ARPE-19
Jin, Andrew, 17
Shedding Light on Human Evolution: Machine Learning Algorithms for
Systematic
Genome-wide Discovery and Characterization of Adaptive Mutations
Kuditipudi, Rohith, 18
Network-based Integration of High Throughput Gene Expression and Methylation
Data
Lin, David, 17
Physical Properties and Evolution of
Lin, David, 17
Physical Properties an... 阅读全帖 |
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l**x
发帖数: 296 | 29 可以因为
1. 高血压，大脑里的aneurysm or angioma. (most common reason)
2。bleeding disorder (出血性疾病：leukemia, thrombocytopenia, hemophilia, or
disseminated intravascular coagulation）
3 Anticoagulant therapy
4 liver disease
5 Cerebral amyloid angiopathy
6 Primary or secondary brain tumors
7. There is also an association with advancing age, male sex, and high
alcohol intake
Bleeding from an intracranial aneurysm or arteriovenous malformation is
primarily into the subarachnoid space, but it may also be partly |
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f******I
发帖数: 769 | 30
or
quite complete differentials, depends on age, most of the time if it's intra
-parenchymal bleed without obvious causes such as on anticoagulant, then it'
s probably amyloid angiopathy, there is nothing you could do about it, |
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y*******8
发帖数: 48 | 33 感谢朋友们的评估！有审稿经验的请传授一下获得审稿机会的法门。如有意转让审稿机
会，请帮忙推荐或联系本人。可以审下属方向的稿件：General molecular Biology,
protein science, protein folding, chaperone, fugal genetics, virology, prion
, amyloid et al.。对不起，最近才想起申请Eb1-a/b，没有注意积累review。目前基
本情况：PhD, 排名10左右大学的non-TT Faculty; 文章一作6（NSC 1）, 其它文章5+,
2 talks, 1 book chapter, 10+ poster; Review 2; 媒体报道10+ ( 多为转载，报道
多为间接，不准备提)，属很弱的case。 顺便问一下， NIH会议的travel
Grant算否？ |
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w*****n
发帖数: 111 | 34 来自主题: Immigration版 - 审稿推荐 有篇 关于“ Amyloid and Prion Fibril Formation Dense Shell Sugar-Decorated
Dendrimers"的文章需要审稿，有兴趣的请和我联系，我会试着推荐。 |
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t****l
发帖数: 445 | 35 我的基本情况：PhD in Theoretical biophysics, 2008. Currently, I have been in
Postdocoral position for 4 years. I am focusing on developing statistical
modeling of protein folding, protein misfolding (such as amyloid fiber
formation), aggregation of bacterial cell and polymer degradation.
If by any chance, I would like to have some 审稿机会 for my application of
green card. Please send email to me n**********[email protected].
多谢。 |
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t****l
发帖数: 445 | 36 My background:
PhD in Theoretical biophysics, I am focusing on developing statistical
modeling of protein folding, protein misfolding (such as amyloid fiber
formation), aggregation of bacterial cell and polymer degradation.
If by any chance, I would like to have some 审稿机会 for my application of
green card.
多谢。 |
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t****l
发帖数: 445 | 37 My background:
PhD in Theoretical biophysics, I am focusing on developing statistical
modeling of protein folding, protein misfolding (such as amyloid fiber
formation), aggregation of bacterial cell and polymer degradation.
If by any chance, I would like to have some 审稿机会 for my application of
green card.
多谢。 |
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s*********r
发帖数: 215 | 38 关键词： Neural Circuits, Neural Plasticity, Neurodegeneration disease,
Alzheimer’s disease,
Channelrhodopsin, amyloid, APP, Dopamine
再攒几篇审稿就可以放心申了，谢谢大家。
有机会请给我站内信。 |
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d******e
发帖数: 1424 | 39 When: 8:00 am – 5:00 pm, Saturday, June 4th, 2011,
Where: Hilton, San Diego/Del Mar (15575 Jimmy Durante Blvd, Del Mar,
CA92014)
Website: http://www.sdbiopharma.org/2011/bio-index.htm
Registration: https://www.123signup.com/event?id=vprmg
$30 per person for early birds registration (valid until May 27); $50 for
regular registration (valid between May 28 and June 1); $80 for onsite
registration (June 4); $10 off any fees mentioned above for students and
postdocs (The fees include... 阅读全帖 |
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d******e
发帖数: 1424 | 40 Program:
8:00 am Continental Breakfast & Registration
8:45 am Welcome
9:00 am Session I. New Frontiers in Life Science
Jeffrey Kelly, Professor, The Scripps Research Institute
‘Transthyretin Kinetic Stabilizers Arrest Peripheral Neuropathy–
A First-in-Class Drug for a Human Amyloid Disease’
Don Jones, VP, Business Development for Health & Life Sciences,
Qualcomm
‘A Sneak Peak at the Future of Wireless Health’
10:30 am Coffee Break
11:00 pm ... 阅读全帖 |
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d***o
发帖数: 341 | 41 转基因和prion是风马牛不相及的东西。
原则上任何蛋白只要找到合适的条件都可以形成amyloid fibrils。
其实prion一般就是起一个种子的作用，诱导蛋白aggregation。我记得prusiner那个组
后来发过一篇文章，将prion注射给老鼠，一些老鼠也出现了一些症状，具体的记不清
楚了，几年前看的了。另外，prusiner的protein only hypothesis并没有一统江湖，
一直还有一些人致力于寻找致病的病毒，好象有个女教授，名字忘了，WIKI上应该搜的
到。
补充一点，有文献中提到血液中也检测到过prion。 |
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x**n
发帖数: 12542 | 42 ☆─────────────────────────────────────☆
mdrealtor (md_realtor) 于 (Wed Apr 25 10:26:56 2012, 美东) 提到:
昨天，看新闻，说美国又发现新的疯牛。
我的问题是，如果把疯牛肉彻底炖烂了，是否还有危险？如果还有危险，为什么呢？我
觉得炖烂了以后，蛋白就没有生物活性了，应该没问题了。
☆─────────────────────────────────────☆
TMR (农业重金属) 于 (Wed Apr 25 10:27:44 2012, 美东) 提到:
I like medium rare.
☆─────────────────────────────────────☆
buckseye (HardHat) 于 (Wed Apr 25 10:36:22 2012, 美东) 提到:
不行，虽然疯牛病病毒是蛋白质病毒，但是此种病毒极耐高温，煮熟也没有。
☆─────────────────────────────────────☆
vn (jmj) 于 (Wed... 阅读全帖 |
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G***a
发帖数: 27294 | 43 （1）insulin intolerance/carbohydrate intolerance/insulin resistance
这几个词都是一个意思。
（2）同时跑步还有一个很大好处，就是产生BDNF（Brain-derived_neurotrophic_
factor）
这是一种神经生长激素---在大脑里，是用来抗衰老的。
而且有一定证据表明，能帮助清除Beta Amyloid。 跑步能促进这种东西释放。
这种东西能提高记忆和空间navigation能力，比如在大停车场里找到你的车。
BDNF还可以抗抑郁。最有效的释放方法：voluntary exercise
PS: 我都被你和大使同化了。。。天天宣传跑步。。。。 |
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G***a
发帖数: 27294 | 44 是，我看得文章说神经毒性，主要是说amyloid Beta
不过要谈起来，又要谈到蛋白剪切，还有酶的问题，中间的pathway太复杂
我也怕说多出错（万一看错了呢）谢谢指正
tau降解之后神经毒性更大，是最近作出来的么？ |
|
G***a
发帖数: 27294 | 45 （1）insulin intolerance/carbohydrate intolerance/insulin resistance
这几个词都是一个意思。
（2）同时跑步还有一个很大好处，就是产生BDNF（Brain-derived_neurotrophic_
factor）
这是一种神经生长激素---在大脑里，是用来抗衰老的。
而且有一定证据表明，能帮助清除Beta Amyloid。 跑步能促进这种东西释放。
这种东西能提高记忆和空间navigation能力，比如在大停车场里找到你的车。
BDNF还可以抗抑郁。最有效的释放方法：voluntary exercise
PS: 我都被你和大使同化了。。。天天宣传跑步。。。。 |
|
G***a
发帖数: 27294 | 46 是，我看得文章说神经毒性，主要是说amyloid Beta
不过要谈起来，又要谈到蛋白剪切，还有酶的问题，中间的pathway太复杂
我也怕说多出错（万一看错了呢）谢谢指正
tau降解之后神经毒性更大，是最近作出来的么？ |
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b*s
发帖数: 82482 | 47 amyloid是生命体么？
所以估计就是一个高级神经动物寄生在一堆低级生命体上。 血脑屏障就是明显的柏林
墙一样的设置。
什么Alzheimer啥的都是低级生命体对高级生命体的逆袭。 |
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f***e
发帖数: 43 | 48 大脑的结构是处于不断变化的，跑步跑个一月半月的还能看到大脑发生了变化，有成年
人新学会一种技能还发现大脑新长出很多neuron，看看这个
http://www.apadivisions.org/division-39/publications/reviews/br
大脑是一个没有研究明白的器官，争论肯定就更多了。真有那种无法改变的大脑结构吗
，我非常怀疑。
至于大脑这种差异是怎么造成的，是基因表达造成的，还是别的因素实际上很难界定。
基因表达这个问题本身也很复杂，很多基因的表达有很多调控因子，有些人不得某些遗
传疾病并不是他们没有致病基因，而是因为他们的这种基因处于休眠状态，或者别的更
复杂的机制。比如alzheimer，其中amyloid beta可能是罪魁祸首，普通人也有这种蛋
白，只是alzheimer清理这种蛋白的速度要慢些。为什么？可能是genome的先天差别，
也有可能少于运动，who knows,研究没有搞清楚，non-conclusive。同卵双胞都有同性恋取向的比例是很高，genome完全一样，为什么不是100%？
我觉得看到这些论文，符合逻辑的结论就是，有证据说明同... 阅读全帖 |
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x***a
发帖数: 19 | 49 PI of the lab.
Dr. Stern is a 1973 graduate of Yale University and received his medical
degree from Harvard Medical School in 1978. He spent most of the next 24
years at the College of Physicians & Surgeons of Columbia University in New
York, where he completed an internal medicine residency and a fellowship in
hematology.
Beginning in 1985, he spent two years at Oklahoma Medical Research
Foundation in Oklahoma City before returning to Columbia as an associate
professor in the department of phys... 阅读全帖 |
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m*****n
发帖数: 7450 | 50 http://www.iflscience.com/brain/scientists-selectively-erase-an
Scientists Selectively Erase And Restore Memories
In a groundbreaking new study, researchers at the University of California,
San Diego erased and then reactivated memories by stimulating neurons in the
brains of genetically engineered rats with a series of light pulses that
have been previously shown to strengthen or weaken the connections between
brain cells. This is the first study to be able to directly show that the
strengtheni... 阅读全帖 |
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