Neurodegeneration 3

Question 1

Main issue with current ND treatment?

Answer 1

Most ND have on cure, treatment only alleviates/delays symptoms

Question 2

Main target of ND treatment?

Answer 2

Aggregates

Question 3

Time course for an ND patient?

Answer 3

Usually over 50 with no evidence–> develop minor psychological/behaviour/motor issues–> develop memory loss, or issues with navigation–> begin differential diagnosis–> begin QOL treatments–>delay symptoms treatment–> alleviate symptoms–> palliative care–> death from another casue

Question 4

Do ND kill people?

Answer 4

No, usually smthn like pneumonia

Question 5

What is special about Wilsons Disease?

Answer 5

It can be treated

Question 6

How does someone get Wilsons Disease?

Answer 6

Inherited–> genetic mutation

Question 7

Main cause of Wilsons Disease?

Answer 7

Copper metabolism disease

Question 8

Which protein is mutated in Wilsons disease?

Answer 8

Copper ion transporting P type ATPase (ATP7B)

Question 9

Role of Copper ion transporting P type ATPase (ATP7B)?

Answer 9

Movement of copper ions across the membrane

Question 10

Symptoms of Wilsons disease?

Answer 10

Abdominal pain, dark urine, jaundice, mood changes, rings around edge of cornea, tremor and stiff muscles

Question 11

How is wilsons disease treated?

Answer 11

A copper chelator–> helps remove copper from the body

Question 12

What are two copper chelators used to treat wilsons disease?

Answer 12

Penicillamine and trientine

Question 13

What are the two ways that aggregates are targeted in ND?

Answer 13

Preventing their formation or causing their breakdown

Question 14

What are causes other than aggregates that can cause ND?

Answer 14

Oxidative stress (toxic radicals–> e.g. superoxide)
Mitochondrial damage–> could produce cytochrome C

Question 15

How is aggregate formation prevented?

Answer 15

Target parent protein, stimulate breakdown enzymes, prevent misfolding

Question 16

How are aggregate parent proteins targeted?

Answer 16

Antisense RNA, genetic knockout (CRISPR-Cas9)

Question 17

How is breakdown of aggregates increased?

Answer 17

Increases the action of the proteasome on that specific protein, use antibody treatments

Question 18

Which disease could be treated with antisense RNA?

Answer 18

Huntingtons

Question 19

Which protein is targeted by antisense RNA in huntingtons?

Answer 19

Huntingtin (HTT)

Question 20

Which (failed) treatment of Alzheimers involved gamma secretase inhibitors?

Answer 20

Brought in a gamma secretase inhibitor to reduce the amount of beta amyloid being produced

Question 21

How effective have antibodies against ABeta been in alzheimers?

Answer 21

Reduced cognitive decline by 20-40%

Question 22

How are the antibodies for Azheimers treatment delivered?

Answer 22

Cannula infusion

Question 23

How are alzheimers antibodies believed to work?

Answer 23

Recruitment of microglia

Question 24

Main cause of PD?

Answer 24

Loss of dopaminergic neurons in substantia nigra in pathway to striatum

Question 25

What are parkinsons treatments aimed at?

Answer 25

Restoring dopamine for the normal function of the striatum

Question 26

What are the two kinds of receptor in the striatum?

Answer 26

D1 and D2

Question 27

What are the two pathways running between the striatum and the motor cortex?

Answer 27

Facilitatory, direct pathway, and the inhibitory, indirect pathway

Question 28

Effect of dopamine on the facilitatory pathway between the striatum and the motor cortex?

Answer 28

It enhances it

Question 29

Effect of dopamine on inhibitory pathway between the striatum and the motor cortex?

Answer 29

It inhibits it

Question 30

Which dopamine receptor is targeted by dopamine for the facilitatory pathway?

Answer 30

D1

Question 31

Which dopamine receptor is targeted by dopamine for the inhibitory pathway?

Answer 31

D2

Question 32

Effect of dopamine loss in PD?

Answer 32

Reduced motor cortex activity

Question 33

How can dopamine be increased?

Answer 33

Provide more dopamine or more dopamine precursor, decrease its reuptake, inhibit its breakdown, provide a dopamine agonist

Question 34

Most common parkinsons treatment?

Answer 34

Provide L-Dopa

Question 35

Why is L-Dopa provided instead of dopamine?

Answer 35

L-Dopa can cross the blood brain barrier

Question 36

Main issues with L-Dopa?

Answer 36

It can be converted to dopamine (which cant cross BBB) in the blood

Question 37

Which drug is given alongside L-Dopa to prevent dopamine formation in the blood?

Answer 37

Cabidopa (dopa decarbodylase inhibitor)

Question 38

Side effect of L-Dopa?

Answer 38

Dyskinesia--> severe involuntary movement

Question 39

How is the dyskinesia of L-Dopa treatment managed?

Answer 39

Patients have an "off" time where they dont take any L-Dopa in order to reduce the prevalence of side effects

Question 40

Second treatment aim at PD after L-Dopa?

Answer 40

Inhibit breakdown of dopamine

Question 41

How is dopamine breakdown inhibited?

Answer 41

Monoamime oxidase B (MAOB) inhibitors

Question 42

What is the main MAOB inhibitor?

Answer 42

Selegeline

Question 43

PD treatment after L-Dopa and MAOB inhibitor?

Answer 43

Catechol O-Methyl Transferase (COMT) inhibitor

Question 44

Side effects of L-Dopa?

Answer 44

Nausea and dizziness

Question 45

Side effects of COMT?

Answer 45

Toxicity to liver cells, diarrhoea and sleep disturbances

Question 46

Main COMT used for PD?

Answer 46

Tolcapone

Question 47

How do dopamine agonists work?

Answer 47

Acts directly on dopamine receptors

Question 48

Side effects of dopamine agonists?

Answer 48

Nausea, dizziness, hallucinations, sleep attacks, hypotension

Question 49

Examples of dopamine agonists?

Answer 49

Pramipexole, Ropinirole, Bromocriptine

Question 50

What is deep brain stimulation?

Answer 50

Implanting an electrode into the striatum--> can stimulate it directly and thus stimulate the activity

Question 51

Benefits of deep brain stimulation?

Answer 51

Doesnt have the same side effects of L-Dopa

Question 52

Complications of deep brain stimulation?

Answer 52

Brain hemorrhage, seizures, death

Question 53

Issues with stem cell treatment for ND?

Answer 53

Cost and time