Neurodegenerative disorders

Question 1

Neuronal degeneration is driven by ________

Answer 1

Neuronal degeneration is driven by cellular apoptosis

Question 2

How do prions diseases (transmissible spongiform encephalopathy) spread from cell to cell?

Answer 2

Because accumulations of prions proteins cause a chain reaction of other proteins to misfold by interacting with them, and it jumps from cell to cell

Question 3

How do prions diseases spread from one animal to the next?

Answer 3

By animals eating the brains of the dead animals

Question 4

Prions diseases are the only infectious agents that are just a protein. What separates them from other infectious agents?

Answer 4

All other infectious agents (bacterial & viral) have nucleic acids (DNA or RNA)

Question 5

What does the progression of Huntington’s disease look like in a person? (what age does it begin, what symptoms do they have, when do they die)

Answer 5

The symptoms usually start at 30-50 years old. In the progression of the disease, people have very jerky movements & severe uncoordination. They eventually get dementia and die, about 15-20 years later.

Question 6

What part of the brain does Huntington’s disease attack?

Answer 6

The nuccleus accumbens in the basal ganglia

Question 7

Why is it problematic to have more that 39 repetitions of CAG proteins (glutamine) is the huntington gene?

Answer 7

Because an enzyme recognizes the long filament as problematic, so it cuts the extra glutamines, but those bits are sticky and they aggregate together & form little clumps in the brain - this eventually causes the cells to die.

Question 8

Why is Huntington’s disease so common? What’s the DNA replication mistake that allows more than 39 repetions of CAG proteins?

Answer 8

During DNA replication, there’s a probability that the DNA copying machinery falls off the chromosome and it has to find back its place to continue - this is usually not problematic, but if a chromosome is already long, it goes back in the wrong place

Question 9

1. What disorder does antisense gene therapy treat?
2. How does it work?

Answer 9

1. Huntington’s disease
2. You administer antisense DNA into the spinal chord of patients, which is meant to pair with an mRNA, which prevents it from translating into a protein

Question 10

Parkinsons disease is in part due to the degeneration of _______ neurons in the midbrain, specifically in the _____________ of the basal ganglia

Answer 10

Parkinsons disease is in part due to the degeneration of [dopamine] neurons in the midbrain, specifically in the [substantia nigra] of the basal ganglia

Question 11

1. What is alpha synuclein and how is it related to Parkinson’s disease?
2. What’s the name for the aggregates of alpha-synucleins? Where are they found?

Answer 11

1. It’s expressed in midbrain in dopamine neurons. Abnormal accumulations of alpha synuclein are found in Parkinson’s disease patients
2. Lewy bodies are found in cytoplasm of the cells in midbrain dopamine neurons

Question 12

1. What’s the role of ubiquitin?
2. What’s the name of the specific organelle responsible for this?

Answer 12

1. It’s the protein responsible for destroying old/misfolded proteins & recycling the amino acids
2. Poteasomes

Question 13

1. What’s a parkin?
2. What do mutated/faulty parkins do?

Answer 13

1. It’s a type of ubiquitin
2. mutated parkins don’t prevent misfolded proteins to accumulate and eventually kill the cell, which can lead to Parkinson’s

Question 14

What does “toxic gain of function” mean? Give an example for Parkinson’s disease

Answer 14

When dominant gene mutation produces a protein with toxic effects
Ex: Mutations in alpha-synuclein gene can prevent the protein, when misfolded, from being ubiquitinated

Question 15

Give an example of toxic gain of function in Huntington’s

Answer 15

Mutations in the huntingtin gene can cause the huntingtin protein to misfold

Question 16

What does “toxic loss of function” mean? Give an example for Parkinson’s disease

Answer 16

When recessive gene mutation causes both chromosomes to not have a necessary protein
→ loss of function mutations in the parkin gene can make it unable to ubiquitinate misfolded alpha-synuclein protein

Question 17

Lauraine has muscle rigidity, slow movements, she shakes a lot and she has difficulty walking. She also has frequent sleep & emotional disturbances. What disorder does she likely have and what disorder will she consequentially develop?

Answer 17

She prob has Parkinsons disease, and she will later develop dementia. Poor Lauraine.

Question 18

Does elevating dopamine signalling in the brain work as a cure for parkinsons?

Answer 18

It does alleviate the motor symptoms for some time, but it’s not a permanent solution.

Question 19

What wrong with giving dopamine receptor agonists to treat parkinson’s?

Answer 19

They work for some time but they cause side effects in the peripheral nervous system

Question 20

1. What L-Dopa?
2. How does it treat Parkinson’s

Answer 20

1. It’s the precursor to dopamine that gets converted into dopamine once it crosses the blood-brain barrier
2. Daily injections diminish symptoms for about 5 years, but then levels become all messed up & it becomes inefficient

Question 21

1. In parkinson’s, which parts of the brain are targeted during deep brain stimulation (DBS) or brain lesions?
2. What happens to said brain regions when the substantia nigra dies off?
3. How does DBS help?

Answer 21

1. The globus pallidus & subthalamic nucleus in the basal ganglia
2. When the substantia nigra dies off, they become hyperactive
3. DBS helps to reduce inhibitory input to the thalamus & facilitate movement

Question 22

REMINDER, not question (flip)

Answer 22

The activity in the caudate nucleus also becomes dysregulated when the substantia nigra dies off.

Question 22

What are some symptoms of dementia?

Answer 22

progressive impairments to memory, thinking, and behaviour

Question 23

What are some precursors to dementia?

Answer 23

Neurodegenerative disease, MS, multiple strokes, and repeated brain trauma.

Question 23

Alzheimers occurs in approximately ____ %of the population above the age of 65 and almost ____% of people older than 90 years

Answer 23

Approximately 10 percent of the population above the age of 65 and almost 30 percent of people older than 90 years

Question 23

Besides age, what are some risk factors for the developing of Alzheimers?

Answer 23

Traumatic brain injury, obesity, hypertension, diabetes, and high cholesterol levels

Question 23

How could immunotherapy be a helpful treatment of Alzheimers?

hint: injecting antobodies that bind directly to…

Answer 23

By injecting antibodies that directly bind to Aß protein or Tau protein, marking them for destruction by the immune system

Question 24

The degeneration of which brain areas is linked to Alzheimer’s?

Answer 24

around and within the hippocampus and neocortex

Question 24

How does the malfunction of secretase enzymes play a role in the development of Alzheimers?

Answer 24

In a normal life cycle, secretase enzymes are supposed to cut the extremities of APP (ß amyloid precursor) so that only the healthy part remains. Healthy sections of APP are normally 40 amino acids long: If the secretase enzymes don’t do THEIR JOB properly,, it cuts it to 42 amino acids.. the extra filaments are sticky & they aggregate

Question 25

1. Where are ß amyloid proteins
2. Where do misfolded ß amyloid plaques form

Answer 25

1. They sit in the membrane of a cell
2. They form with glial cells in extracellular space

Question 26

1. What are Tau proteins
2. What disruption leads them to cause Alzheimers

Answer 26

1. they’re proteins that make the microtubule of the cell
2. In Alzheimer’s they become hyper-phosphorylated, which disrupts intracellular transport & causes microtubule to break down

Question 27

What are neurofibrillary tangles

Answer 27

They’re accumulations of tau proteins - they form next to amyloid plaques. Seen in dying neurons

Question 28

How does the mutation of presenilin cause early onset Alzheimers

Answer 28

Presenilin is a mutation of secretase that always cute ß amyloid proteins wrong, which causes Alzheimers to develop earlier

Question 29

Why are people with Downs syndrome predisposed to develop Alzheimers early in life

Answer 29

Because the gene for APP protein is located on chromosome 21 (the one ppl with Downs syndrome have an extra copy of), so they get more chance for secretase to malfunction

Question 30

1. What is the apolipoprotein E (ApoE) protein?
2. Which version of the ApoeE causes increased risk of early onset Alzheimers?

Answer 30

1. It’s a protein that normally regulates presence of cholesterol in the blood & plays a role in cellular repair
2. People with version E4 have an increase rate of early onset Alzheimers

Question 31

List the 3 factors for development of early onset alzheimers (just list them don’t explain)

Answer 31

1. Presenilin mutation
2. Downs syndrome
3. Version E4 allele of ApoE protein

Question 32

Generally, what does Lou Gehrig’s disease/ALS do to the body?

Answer 32

It attacks motor neurons in spinal & cranial nerves

Question 33

___% of Lou Gehrig’s /ALS causes are sporadic, while ___% are inherited from parents

Answer 33

90% of Lou Gehrig’s /ALS causes are sporadic, while 10% are inherited from parents

Question 34

What’s the incidence of Lou Gehrig’s disease&? (ALS)

Answer 34

3 in 100,000 people

Question 35

What are the symptoms of ALS/Lou Gehrig’s disease?

Answer 35

Spasticity (increased muscle tension causing stiff, awkward movements), exaggerated stretch reflexes, progressive weakness and muscular atrophy, followed by paralysis and then death.