Neurodegenerative Diseases

Question 1

What is multiple sclerosis (MS)?

Answer 1

It is an autoimmune demyelinating disease. The person’s immune system attacks myelin sheaths, leaving behind hard patches of debris called sclerotic plaques. Normal transmission interrupted

Question 2

What is the usual pattern in MS at the start of the disease?

Answer 2

Remitting-relapsing MS. Aka Increase in activity followed by decrease.

Question 3

What follows the remitting-relapsi g MS later in the course of the disease?

Answer 3

Progressive MS: slow, continuous increase in the symptoms of the disease

Question 4

Important facts/causes to know about MS

Answer 4

-generally sporadic disease: no caused by inherited gene mutation
-More diagnosis in women than men
-more diagnosis in people who spent childhood far from equator (hygiene hypothesis: if not exposed to virus as a child, immune system will get confused if gets it)
-more diagnosis in people born in late winter and early spring

Question 5

Drugs that can help with MS

Answer 5

-interferon beta: protein that modulates responsiveness of immune system
-glatiramer acetate: peptides that mimic myelin

But note that can just help, cannot completely stop disease.

Question 6

What’s common in all neurodegenerative diseases?

Answer 6

Neurons are undergoing apoptosis

Question 7

What triggers apoptosis?

Answer 7

Collections (aggregates) of misfolded proteins that disrupt normal cellular function.

At some rate, proteins midfold. And then there is more chance of clumping up. The brain knows how to deal woth it but not always. When they aggregate, becomes more and more difficult to clear away.

Question 8

What is transmissible spongiform encephalopathy?

Answer 8

A family of rare contagious brain disease (includes mad cow and Creutzfeldt-Jacob) whose degenerative process gives the brain a sponge-like appearance.

Question 9

What causes transmissible spongiform encephalopathy?

Answer 9

The accumulation of misfolded prion protein. Prion proteins have the ability to transmit their misfolded shape onto healthy variants of the same protein.

Ex. Dangerous to eat animal brain because chance of eating misfolded prion protein.

Question 10

What symptoms characterize huntington’s disease?

Answer 10

An increasingly severe lack of coordination, uncontrollable jerky limb movements, and eventually dementia followed by death.

Question 11

What causes Huntington’s disease?

Answer 11

One dominant mutation in the Huntingtin gene (long huntington). Some people have a mutation in huntington that makes it more likely to aggregate. Heavily expressed in the basal ganglia, causing neurodegeneration (basicaly no basal ganglia left)

Question 12

How many people are affected by hungtington’s disease in the population?

Answer 12

1/10,000 people

Question 13

Is there a cure for huntington’s disease?

Answer 13

No, but optimism about potential of antisense gene therapy.

Antisense gene therapy: Inject antisence DNA, binds with long huntington’s before it gets translated into a protein, so bad huntington gets degrated before being translated.

Question 14

What if parkinson’s disease associated with?

Answer 14

The degeneration of dopamine neurons in the midbrain

Question 15

Percentage of pop affected by parkinson

Answer 15

1%

Question 16

How can we explain the death of dopamine neurons in parkinson’s disease?

Answer 16

The protein alpha-synuclein, which is heavily expressed in dopamine neurons, tends to aggregate at some rate. Overtime these protein aggregates cause dopamine neurone to undergo apoptosis

Question 17

How to we call the aggregate of alpha-synuclein protein?

Answer 17

Lewy body

Question 18

What is ubiquitin

Answer 18

The protein that is put on misfolded proteins, to target them for degradation.

Question 19

What is parkin

Answer 19

Protein that flots around and recognizes misfolded proteins. When it does, attaches ubiquitin molecule to it.

Cause of familial parkinson’s disease. If parkin is defective, misfolded proteins accumulate, aggregate, and eventually fill the cell

Question 20

What is the first treatment for parkinson’s disease?

Answer 20

L-dopa injections.

Dopamine does not cross blood brain barrier so it cannot be taken as a medicine to boost brain dopamine levele. However, a precursor of dopamine, L-dopa can enter the brain where it is readily converted to dopamine. L-dopa treatments diminish the motor symptoms of PD

Question 21

What is the second treatment for PD when there is too few dopamine neurons for L-dopa injection to be effective

Answer 21

Deep brain stimulation in parts of basal ganglia. Most popular spot to stimulate is subthalamic nucleus.

Question 22

Dementia

Answer 22

Progressive impairments to memory, thinking and behavior that affect the ability to perform ecerydqy activities

Question 23

Most common form of dementia

Answer 23

Alzheimer’s disease

Question 24

How common is alzheimer

Answer 24

Very common. 10% of 65+, 50% of 85+.

Question 25

What is alzheimer associated with

Answer 25

Aggregates of misfolded beta-amyloid protein all around the brainz many less neurons.

Question 26

Whats the name of the class of enzymes that cuts Beta-amyloid precursor protein into smaller fragments, including beta-amuloid

Answer 26

Secretase

Question 27

Whats the protein that forms part of the secretases that cut APP. Mutations in that protein cause it to generate abnormal long form beta-amyloid, which causes early onset Alzheimer’s disease

Answer 27

Presenilin

Question 28

How do we call the aggregation of beta-amyloid protein?

Answer 28

Amyloid plaque

Question 29

How do we call the part of the microtubule that gets hyper-phosphorylated

Answer 29

Tau protein

Question 30

Neurofibrillary tangle

Answer 30

Intracellular accumulation of twisted Tau protein in dying neurons

Question 31

Recap alzheimer disease

Answer 31

If you have a bad presenilin going around cutting beta-amyloid protein at wrong place, it’s gonna build up faster that you can clear it away. In alzheimer patients, beta-amyloid is found in accessive amounts, the aggregation of that protein is called amyloid plaque. And what happens next is that the tau protein that is part of the microtubule gets hyper-phosphorylated, and thus the microtubule system breaks apart. And we get neurofibrillary tangle

Question 32

So what are the two main problems we see when we cut the brain of alzheimer patients?

Answer 32

1- aggregation of amyloid plaques
2- big clusters of misfolded microtubules (neurofibrillary tangles)

Question 33

Is there a cure for alzheimer disease? If not, what is the mosy promising one?

Answer 33

No, but promising approach is immunotherapy: getting antibodies to recognize and destroy Abeta protein (or tau protein, or both)

Question 34

Symptoms of amyotrophic lateral sclerosis (ALS) + how many people are affeced

Answer 34

Spasticity, exaggerated stretch reflexes, progressive weakness and muscular atrophy, ans finally, paralysis. 3 in 100 000 people