Prion在线视频

Hi, welcome back. I'm Yun Su,
欢迎回来，我是来自

from Shantou University
汕头大学

Medical College.
医学院的苏芸老师

In this chapter,
在本章节中

we are going to share with you
我们一起来学习

a special pathogen — prion.
一种特殊的病原体——朊粒

Are you ready?
大家准备好了吗？

Here are the learning
以下是本节课的

objectives for you.
学习目标

1. Describe the biological properties
1. 描述朊粒的生物学性状

and pathogenesis of prion;
和致病机制

2. Know how to make a diagnosis,
2. 懂得如何诊断

treat, prevent,
治疗、防控

and control prion diseases;
朊粒病

3. Compare traditional viruses
3. 比较病毒

and prions.
和朊粒的特点

Well, we will draw your attention
我们先来看

to a case.
一个案例

A 65-year-old woman presented
女性，65岁

with a recent onset
最近感到

of overt weakness,
明显虚弱

forgetfulness, difficulty speaking,
出现健忘，言语困难

and involuntary movements
右臂不自主运动

of her right arm. Three months later,
三个月后

she was hospitalized due
她因肌肉阵挛性发作

to myoclonic seizures
及其他神经系统症状

and other neurologic signs.
入院

In her cerebrospinal fluid (CSF),
脑脊液检查

a protein called “14-3-3”
显示“14-3-3”蛋白

was detected,
阳性

with no evidence
但未发现其他感染

of an infection.
的证据

The patient's condition continued
患者的病情

to deteriorate,
持续恶化

she went into a coma,
之后陷入昏迷

and died 4 months
患者在发病后的

after the onset of symptoms.
4个月死亡

At autopsy,
尸检结果显示

brain sections showed vacuolation
脑组织出现空泡变性

and amyloid-containing plaques
淀粉样斑块形成

and fibrils, no inflammatory
和纤维增生，未发现

cells were found.
炎性细胞浸润

These are questions you
请思考

need to think about:
以下几个问题

1. What clinical manifestations
1. 朊粒病的临床表现

indicate a prion disease?
有什么？

2. What are prions ?
2. 什么是朊粒？

3. What lab tests could be used
3. 有什么实验室

for diagnosis?
诊断方法？

I hope you can find
希望大家

the answers after this session.
课后能找到答案

First, we should know
我们先来了解

more about prion.
朊粒

Prion is a term derived from
朊粒一词来源于

“proteinaceous infectious particle”.
“传染性蛋白颗粒”

It refers to the infectious agent
它是一种具有传染性的

consisting only of mutated protein
变异蛋白

without nucleic acid genome,
与典型的病毒不同

unlike a typical virus.
它不含核酸

Prions are responsible for
朊粒是导致

transmissible spongiform
传染性海绵状脑病（朊粒病）

encephalopathies (prion diseases).
的病原体

These diseases can be sporadic,
这种疾病可为散发性

inherited or acquired,
遗传性或经传染获得

comprising multiple conditions
可在人类

that can affect both humans
与动物中引起

and animals.
多种朊粒病

Let’s discuss more
接下来我们学习

about the general properties.
朊粒的生物学性状

Normally,
正常情况下

there is the normal protein
人体内

termed PrPc (cellular prion protein)
存在着正常的细胞朊蛋白

in humans,
PrPc

encoded on chromosome 20.
该蛋白由第20号染色体所编码

Under certain conditions,
在一定条件下

PrPc converts into an isoform
PrPc发生构象变化

with an aberrant conformation
转变成一种

(misfolded protein).
异构体（错误折叠的蛋白）

That is PrPsc
即 PrPsc

(Scrapie isoform of PrP),
（羊瘙痒病朊蛋白）

as you can see in the picture.
从图中大家发现

What are differences
PrPc和PrPsc

between PrPc and PrPsc?
有什么不同？

As shown in the table,
如表格所述

PrPc has mainly α-helical
PrPc的空间构象主要以α螺旋为主

with little β-sheet content.
很少β折叠

It is protease sensitive,
它对蛋白酶敏感

and is held in the cell membrane.
并表达在细胞膜上

PrPsc is a mutated protein
PrPsc是一种构象异常的蛋白

enriched with β-sheet.
主要以β折叠为主

It tends to form aggregates
它常形成聚集物

and amyloid fibrils.
和淀粉样纤维斑块

PrPsc is resistant
PrPsc对多种

to a wide range of chemical
理化因素

and physical treatments,
具有强抵抗力

such as protease, formaldehyde,
例如蛋白酶，甲醛

ultraviolet radiation,
紫外线照射

and heat up to 80°C.
80℃加热

It is cell free,
它不依赖细胞存在

existing in the cytoplasmic vesicles
可出现在胞质空泡中

or extracellular milieu.
或细胞外环境中

How does prion cause disease?
朊粒是如何引起疾病的？

Once a PrPsc  aggregate
当 PrPsc 聚集物

has been formed,
形成后

it acts as a template
它可以作为模板

and passes on its conformation
诱导（PrPc）发生构象改变

to each new PrPsc perpetuating
转化成PrPsc

the change,
这种变化过程

similar to a mutation of a virus.
有些类似于病毒的变异

Aggregation of prions may cause
朊粒的聚集

or contribute to human diseases.
可导致人类疾病

Actually, prion disease
实际上, 朊粒病

may be inherited or transmitted
可以遗传或

via infected tissue.
通过感染组织传染

Prion infection can occur:
朊粒的传播途径有：

1. by ingestion，
1. 通过进食

2. through breaks in the skin，
2. 通过皮肤伤口

3.via transplantation
3.通过移植

of contaminated tissues
被污染的组织

(e.g., cornea)，
（如角膜）

4.by use of contaminated
4. 通过使用被污染的

medical devices.
医疗器械传播

After the acquisition of the prion,
感染朊粒后

what will happen next?
会发生什么？

1.The prions accumulate in the
1.朊粒会在功能削弱的

highly enervated secondary
次级淋巴组织

lymphoid tissues.
中聚集

2.They travel up the neurons
2. 进而沿着神经元侵入

to the central nervous system
中枢神经系统

and the brain.
和大脑

3.The PrPsc reaches high
3. PrPsc在大脑

concentrations in the neurons
神经元和吞噬细胞中

and phagocytic cells in the brain.
高浓度聚集

It is difficult to degrade,
聚集物难以被降解

contributing to the cerebral
从而导致大脑

pathological changes —
发生病理改变（海绵状脑病）

spongiform encephalopathy .
海绵状脑病

Spongiform encephalopathy
海绵状脑病

is characterized by
的特点是

of the vacuolated neurons
神经元和

and adjacent glial cells,
附近的胶质细胞发生空泡变性

amyloid plaques and fibrils,
有淀粉样斑块和纤维形成

the proliferation of astrocytes,
星形胶质细胞增生

with no immune response
但没有炎症反应

or inflammation.
或免疫应答的发生

The disease of transmissible
传染性

spongiform encephalopathy
海绵状脑病

shows the following characteristics:
有以下特点

1.It is a progressive,
1.该病是一种进行性加重的

degenerative neurologic disease
中枢神经系统退行性变

with a long incubation period
伴有很长的潜伏期

(as long as 30 years).
（长达30年）

2.It is fatal with rapid progression
2.这种疾病具有致死性

to death after the onset
一旦发病，病情进展迅速

of symptoms.
最终导致死亡

3.There is no detectable
3. 疾病中无

immune response.
免疫应答的发生

4.The major manifestations
4.疾病的主要临床表现包括

of the disease include a loss
肌肉运动失控

of muscle control, shivering,
颤抖

myoclonic jerks and tremors,
肌阵挛性抽搐，震颤

loss of coordination,
共济失调

rapidly progressive dementia
进行性痴呆

and death.
以及死亡

Now, let’s look at the types
现在，让我们来看看

of prion diseases.
朊粒病的类型

As shown in the table,
如表格所示

prion diseases comprise multiple
人类和

conditions that can affect both
和动物的朊粒病

humans and animals.
有多种

The most well-known human prion
最常见的人类朊粒病

disease is Creutzfeldt-Jakob
是克-雅病(CJD)

Disease (CJD) and its variations.
以及变异型克-雅病

In animals, they are Scrapie (Sheep)
主要的动物朊粒病有

and Bovine Spongiform
羊瘙痒病

Encephalopathies (BSE commonly
和牛海绵状脑病

known as Mad Cow Disease).
（也叫疯牛病）

CJD is a good example
人类朊粒病的代表性疾病

of human prion disease.
是克雅病

The picture here shows
图片展示的是一位患有

an old man with CJD.
克雅病的老年患者

It usually affects persons
该病好发于

older than 50 years.
50岁以上的人群

It may start with decreased
疾病的临床表现包括

memory and dementia,
记忆力减退和痴呆

irregular jerking movements,
不规则肌阵挛

progressive muscle function
进行性肌肉功能减退

loss and death. Moreover,
以及死亡，另外

the brain sections show
大脑组织切片显示

the characteristic
特殊的

spongiform appearance.
海绵状病变

At this time,
现在

we’ll make a summary
我们来总结一下

about pathogenic characteristics
朊粒病

of prion disease:
的致病特征

1.No cytopathologic effect
1. 朊粒无致

in the cells;
细胞病变效应

2.Long doubling time of
2.倍增时间较长

at least 5.2 days;
至少5.2天

3. Long incubation period；
3. 疾病潜伏期长

4. Causes vacuolation of neurons
4. 病理表现为神经元空泡变性

(spongiform), amyloid-like plaques,
（海绵状），淀粉样斑块形成

gliosis；
神经胶质增生

5.Causes loss of muscle control,
5. 临床表现为肌肉运动失控

shivering, tremors, dementia；
阵挛，震颤，痴呆

6.Lacks antigenicity, inflammation,
6.朊粒无免疫原性，不能刺激炎症反应

immune response.
和免疫应答

Next, we will go to the question
接下来，我们来看看

of what lab tests could be used
有什么实验室

for diagnosis?
诊断方法？

There are no methods
目前尚无检测组织中

for direct detection in tissue,
朊粒的直接方法

and there is no serologic response.
血清学检查诊断意义不大

The initial diagnosis is based
初步诊断可以

on the clinical picture and magnetic
根据临床表现与

resonance imaging.
核磁共振成像结果

Combined with some lab tests,
进一步确诊

a confirmatory diagnosis
需要结合一些

can be made.
实验室检查

The commonly used lab
常用的实验室检查

tests include:
包括

1.detection of elevated levels
1.检测脑脊液中升高的

of 14-3-3 protein or tau protein
生物标记物14-3-3蛋白或者

in CSF;
tau蛋白

2.western blot detection
2.免疫印迹检测

of proteinase K-resistant form
扁桃体活检组织中

of in a tonsil biopsy;
对蛋白酶K有抗性的PrP

3.detection of amyloid plaques,
3. 病理检查脑组织中的淀粉样斑块

spongiform vacuoles,
海绵状空泡变化

and immunohistological
免疫组化

identification of PrP at autopsy.
检测 PrP

Here are pictures showing
这些图片展示了

neuropathological features:
疾病中神经系统的病理学特征

amyloid plaques surrounded
尸检显示脑组织

by vacuoles(spongiform changes)
淀粉样斑块形成

in the post mortem examination
周围的神经元空泡变性

of the brain,
（海绵状改变）

and prion protein
免疫细胞化学检测

accumulation by
显示朊蛋白

immunocytochemistry.
聚集

OK, after we make the diagnosis,
诊断明确后

what can we do?
应该怎么处理？

We can adopt some measures
我们可以采取一些

for management and prevention.
处理和预防措施

Unfortunately,
朊粒病

prion diseases cannot be cured.
无法治愈

There is no known effective
目前对朊粒病无有效的治疗方法

treatment and no vaccine available,
也无可接种的疫苗

but certain medicines
但是一些药物

may help slow their progress.
可以延缓病程

So management largely focuses
所以朊粒病的处理主要是

on supportive care.
支持性治疗

For prevention and control,
在防控措施中

proper sterilization of medical
医疗器械的灭菌

equipment is very helpful.
非常重要

Disinfection procedures
灭菌过程

should be meticulously carried out.
必须细致彻底

Overall safety measures
保障输血

of blood and blood
和血制品的安全

product transfusion,
以及

and organs or tissue
器官和组织移植物安全

transplantation are necessary.
也是必要的预防措施

Moreover, new regulations
此外，一些新制定的

which govern the handling
饲养和处理动物的

and feeding of animals such as:
管理条例例如

1.ban on meat and bone meal
1.禁止用使用动物骨肉粉

in animal feeds，
喂养牛、羊

2.testing of slaughtered animals，
2.严格检测动物制品

3.universal disposal
3.合理、彻底的处理

of "high-risk materials"
动物尸体中的

from carcasses
“高感染风险物质”

may help impede the spread
可以阻止朊粒病

of prion diseases.
的传播

One the whole, the outbreaks
总之，由于

of BSE and variant CJD(vCJD)
疯牛病和变异型克-雅病

in some countries
在一些国家的爆发

had instigated legislations
促进了相关法规的落实

and encouraged more careful
也加强了对动物牲畜的

monitoring of cattle.
监测工作

Recognition of BSE transmission
通过对疯牛病传播途径的认识

routes enables the establishment
我们建立了

of “protective wall” .
“防护墙”

If protective wall works effectively,
如果“防护墙”足够有效

no infectious materials
传染性病原因子

can enter the food chain,
将无法进入食物链

the disease can be prevented
由此防止朊粒病的发生

and ultimately brought
人类也将最终很好地

under control.
防控这种疾病

Let’s recall the questions
现在我们来回忆一下

of the case again.
在之前案例中提出的问题

1. Which clinical manifestations
1. 朊粒病的临床表现

indicate a prion disease?
是什么？

2. What are prions ?
2. 什么是朊粒?

3. What lab tests could be used
3. 什么实验室检查

for diagnosis?
可用于诊断？

I believe it is easy for you
相信这些问题

to answer these now.
都不难回答

Before we finish,
下课之前

there is one more question.
还有一个问题

What are the differences
朊粒

between prions and
和普通病毒

the traditional viruses?
有什么不同

The table here gives you
下面的表格会

the answer.
给出答案

Please review as it will improve
请复习这个表格

your understanding.
由此帮助大家更好地理解

Thank you for your participation!
谢谢同学们的参与

Hope you have
希望大家

enjoyed this session.
喜欢这节课的内容

Here are the references
这些是引用文献

and websites cited.
和相关内容的网址