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a)L-DOPA is a drug that i sused in thr formation of dopamine. Dopamine stimulates movement signals in the neuortransmitters, this reduces the chances of developing Parkinson's diseae.

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a)L-DOPA is a drug that i sused in thr formation of dopamine. Dopamine stimulates movement signals in the neuortransmitters, this reduces the chances of developing Parkinson's diseae.

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b) Selegeline is an inhibitor of monoamine oxidase-B that inhibits the function of dopamine through the process of breaking it down.

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1a) L-DOPA drug is used in formation of dopamine. Dopamine is a hormone that   facilitates movement regulation in the brain. They help to reduce Parkinson's disease symptoms through facilitating movement signals in neurotransmitters.

b) Selegeline, which is an inhibitor of monoamine oxidase-B, which is a substance that inhibits the function of dopamine, by breaking dopamine down. Without MoA, there is more dopamine available to facilitate movement regulation in the brain.

c) Tolcapone inhibits the enzyme that breaks down dopamine

d) Ropinirole promotes the function of dopamine

e) Safinamide inhibits the enzyme that breaks down dopamine, which allows dopamine to function for longer periods of time.

2a) Since stem cells are able to differentiate into any cell types, stem cells can be differentiated into dopamine-producing neurons, which is something that patients with Parkinson's disease are unable to do optimally.

2b) Stem cells can be used in gene therapy by replacing mutated/ damaged cells with newly-differentiated stem cells.

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1a) the lack of dopamine is replaced by the conversion of L-dopa to dopamine through the use of dopa decarboxylase

1b) the dopamine lasts longer because of elegeline, which inhibits the mao-b enzyme that breaks dopamine down

1c) to allow more dopamine to be created from l-dopa, tolcapone inhibits the enzyme which breaksdown l-dopa. it allows levopoda in the body to last longer.

1d) the agonist allows receptors to be activated

1e) dopamine stays in the body for a longer period of time

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1a) L-DOPA is a drug that is changed into dopamine by brain cells with the use of dopa decarboxylase. Dopamine stimulates movement signals in the neurotransmitters, which reduce the symptoms of Parkinson's disease.

1b) Selegeline decreases the dose of levodopa needed to control symptoms by increasing the amount of dopamine by inhibiting MAO-B. MAO-B breaks down dopamine, so selegeline prevents the break down of dopamine.

1c) Tolcapone increases levels of levopoda in the body by blocking COMT enzyme and acting as an inhibitor to prevent the breakdown of levopoda in the body. It makes it so levopoda lasts longer in the body.

1d) Ropinirole can act as a substitute for dopamine and can mimic the functions of dopamine.

1e) Safinamide is a monoamine oxidase B (MAO-B) inhibitor. It blocks an enzyme in the brain that breaks down dopamine, allowing dopamine to work for a longer period of time.

2a) Stem cells have the ability to differentiate into many specific specialised cells. The usage of stem cell therapy allows stem cells to differentiate into normal neurons that secrete normal amounts of dopamine in the body and can replace the abnormal neurons.

2b) Gene therapy is the introduction of healthy genes into the cells of the Parkinson's patient, and replace the mutant gene with healthy genes. This makes it so that the proteins produced by the neuron cells are altered and become normal.

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1)
(a) L-dopa is taken up by remaining dopaminergic neurons where it undergoes decarboxylation in the presynaptic terminal to form dopamine.

(b) selegiline is a selective monoamine oxidase B (MAO-B) inhibitor. MAO-B is an enzyme that breaks down dopamine in the brain. By inhibiting the action of the MAO-B enzyme, Eldepryl leads to an increase in the amount of dopamine.
(c) By inhibiting catechol-O-methyltransferase (COMT), tolcapone further decreases the degradation of levodopa in the periphery, which allows more levodopa to reach the brain and potentially allows for a decrease in the dosage of levodopa.
(d) Ropinirole has a high affinity for and stimulates the post-synaptic dopamine receptors D2 in the central and peripheral nervous systems.
(e) Safinamide is a selective, reversible monoamine oxidase type B inhibitor. It also inhibits the release of glutamate, a substance that may have a role in motor fluctuations.
2)
(a) Stem cells have the potential for self-renewal through unlimited replication, as well as the capacity to differentiate into any cell type within the body. The ability to direct the fate of these cells to become a dopaminergic neuron potentially, therefore, offers an unlimited number of cells that could be used for neural grafting.
(b) Gene therapy is a category of treatments that involve introducing DNA into cells in an effort to alter which proteins are created and thereby improve symptoms or even cure disease.

1) -75mV
2) -30 mV because it is just before the steep incline of depolarisation. any
3)

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Data-based questions: Parkinson’s disease

1a) L-DOPA drug is used in formation of dopamine catalyzed by dopa decarboxylase. Therefore, dopamine will be created do the dopamine will increase. This will improve the symptoms of Parkinson’s disease.

b) Selegeline will slow down and prevents the break down of dopamine by inhibiting MAO-B from breaking down dopamine.

c)Tolcapone will slow down the break down of intermediate of dopamine by inhibiting COMT

d)Ropinirole will promote the function and activity of dopamine so this will support the movement.

e) Safinamide prevents the uptake so dopamine is not breakdown, and the levels od dopamine will increase which remains high in synapse. This will make the movement normal.

2a) Stem cells can differentiate and develop into normal neuron which can be replace the damaged neuron. (dopamine secreting neurons).

However, using embryotic stem cell is not ethical compare to adult stem cell.

b) Gene therapy can transfer the required gene and replace mutant gene. In this case, required gene is dopamine producing gene. Therefore, by transferring dopamine, cell can produce dopamine normally.

However, there is no guarantee that this will work, and it might cause a harmful DNA mutation and might transfer some toxic to the body.

Data-based questions: Analyzing an oscilloscope trace

1)    -73mv

2)    -30mv membrane potential starts to increase very steeply and need sodium ions to diffuse sodium channels to depolarize the membrane.

3)    Time taken for depolarization-approximately 3ms

Time taken for repolarization-approximately 4ms

4)    More than 66ms as the graph haven’t reach to the resting potential yet.

5)    12action potentials per seconds. Because in one second, there is 1000ms. In one action potential. It occurs every 80ms before it goes back to the resting. Thus,1000/80=12 action potentials per seconds.

6)    Presence of potassium ions in the membrane. Some of the positive ions are still detected in the membrane which causes the membrane potential to rise after the repolarization.

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1. (a) The addition of L-DOPA would form more dopamine with the use of dopa decarboxylase. As Parkinson's disease is caused by dopamine deficiency as a neurotransmitter, the increase in dopamine relieves the symptoms.

b) Selegeline inhibits MAO-8. MAO-8 is responsible for the breaking down of dopamine, meaning that if it were inhibited, there would be an increased amount of dopamine, hence relieving Parkinson's symptoms.

c) Tolcapone inhibits COMT. COMT breaks down L-DOPA, preventing it from forming dopamine. By inhibiting this enzyme, it increases the concentration of L-DOPA, allowing for a higher rate of production of dopamine.

d) Ropinirole is an agonist of dopamine. This means that it has the same effect as dopamine on the synapses of the brain, hence alleviating the symptoms of Parkinson's disease.

e) Salfinamide inhibits the uptake of dopamine by presynaptic neurons. This increases the concentration of dopamine in the synaptic cleft, allowing it to bind to the receptors of the post-synaptic neuron, hence alleviating the symptoms of Parkinson's.

2. a) Stem cells can be specialised to form neurons that are able to secrete dopamine properly, replacing the abnormal neurons that are unable to.

b) Gene therapy can be used to produce neuron cells that are able to properly secrete dopamine. As these cells reproduce, they will produce and secrete more dopamine, replacing the faulty neurons.

1. -75mv

2. -30 mv. After this voltage, the voltage shows an increased rate of increase, showing that the sodium ions are able to flow through the opened voltage gated channels.

3. 20ms

4. More than 75ms, as the graph has not reached the resting potential after repolarization.

5. Less than 13. As there are 1000ms in a second, the time taken from the start of the opening of sodium voltage gates to the end of the graph is 75ms, which allows for 13 action potentials. However, the graph has not reached the hyperpolarization period, hence meaning that each cycle would result in longer than 75ms.

6. Active transport takes place to redistribute the potassium and sodium ions.

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1.

a) L-dopa: Dopa decarboxylase decarboxylates L-DOPA to become Dopamine.

b) selegeline, which is an inhibitor of monoamine oxidase-B (MAO-B): Selegeline inhibits dopamine.

c) tolcapone, which is an inhibitor of catechol-O-methyl transferase (COMT): Tolcapone inhibits L-DOPA and a product of dopamine.

d) ropinirole, which is an agonist of dopamine: Instead of inhibiting dopamine, ropinirole promotes the production of dopamine.

e) safinamide, which inhibits reuptake of dopamine by presynaptic neurons: Safinamide inhibits the reuptake of dopamine and extends the duration of its effect.

2.

a) stem cell therapy: Neurons that don’t function properly in Parkinson’s disease can be replaced by neurons produced through stem cell therapy. The biggest problem with this is mainly ethical in that some people question whether some stem cell procedures are ethical or not.

b) gene therapy: Through gene therapy, the actual DNA of an individual with Parkinson’s disease might be able to be altered in such a way that lets the individual’s neurons function again. This might mean retrieving healthier genes from other organisms, which could, again, bring up ethical issues as well as damage the DNA as a result of human error.

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1. (a) L-dopa: L-dopa can undergo decarboxyalation to form dopamine by DOPA decarboxylase. This helps
(b) Selegeline: It is a inhibitor of monoamine oxidase that is irreversible, otherwise, an enzyme that
catabolizes dopamine. It helps control the symptoms of L-dopa.
(c) tolcapone: it is an inhibitor of catechol-O-methyl transferase which also is supplementary to L-dopa as it acts
as a inhibitor of L-Dopa and is a produced from dopamin.
(d) Ropinirole: This would induce the production of dopamine by mimicking the functions of dopamine in the
brain, thus, can be used as a substitute at low levels of dopamine.
(e) Safinamide: This treatment is an add-on to the L-dopa treatment whereby it would inhibit dopamine whilst the
effects is kept prolonged.

2. (a) There are dysfunctional neurons, which cannot produce dopamine, involved in Parkinson's disease which can
be helped to be replaced through stem cell therapy as stem cells can differentiate into specialized cells and
reproduce large number of cells.
(b) The aim is to directly deliver particular genes to the neurons where it is affected to help the neurons recover.
It involves receiving genes from another person with healthier genes which has some ethical considerations that
need to be taken into account.

Source:
https://proteopedia.org/wiki/index.php/DOPA_decarboxylase
https://www.ncbi.nlm.nih.gov/books/NBK526094/
https://parkinsonsnewstoday.com/requip/
https://www.dovepress.com/safinamide-in-the-management-of-patients-with-parkinsonrsquos-disease--peer-reviewed-fulltext-article-TCRM
https://www.dvcstem.com/post/stem-cell-therapy-for-parkinsons
https://www.epda.eu.com/living-well/therapies/surgical-treatments/gene-therapy/

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1. (a) L-Dopa would cause a formation of dopamine into the brain which would then be catalysed by dopa decarboxylase. Dopamine is a naturally occurring substance that is needed to control movement and its levels are reduced in people with Parkinson's.
(b) Selegeline inhibits MAO-B which help prevents the breakdown of dopamine in the brain.
(c) Tolcapne which inhibits COMT, which promotes the activity of neurotransmitter dopamine, which helps regulate movement.
(d) Ropinrole undergoes the same mechanism as dopamine, which can be used in early and late parkinsons.
(e) Safinamide inhibits the release of glutamate, a substance which may have a role in the motor functions.
2. (a) Stem cell therapy can help by replacing lost dopamine-producing neurons, which decay as the disorder advances.
(b) Gene therapy has the potential to alter the way neurons in the brain work. This can help overcome parkinsons by

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1a) L-DOPA would form dopamine and would be catalysed by dopa decarboxylase. The formation of dopamine would then help improve the Parkinson's symptoms as Parkinson's deals with the loss of dopamine.
1b)

2a) A cure for Parkinson's would be stem cell therapy. Using stem cell therapy, the dead nerve cells can be replaced with living, dopamine-producing ones. This would then improve the symptoms of Parkinson's.
2b) Gene therapy would also help overcome Parkinson's as if we change the base sequence in the gene that codes for the loss of dopamine, we would be able to then increase the dopamine levels.

1a) -75mV
1b)
1c) Time taken for depolarisation would be

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1) L-Dopa gets broken down to form dopamine by dopa decarboxylase, which in one of the neurotransmitters in the brain. As parkinson's involves the loss of dopamine production, the formation of dopamine by L-Dopa alleviates parkinson's.
b) selengeline inhibits MAO-B. MAO-B breaks down dopamine, reducing the amound of dopamine in the body. As parkinson's involves the loss of dopamine production, the inhibition of dopamine break-down increases the dopamine content in the body, alleviating parkinson's.
c) tolcapone inhibits COMT, which breaks down L-Dopa. As L-Dopa alleviates parkinson's by increasing dopamine content, the inhibition of L-Dopa break-down increases the L-Dopa content in the body, which increases dopamine content and alleviates parkinson's.
d) ropinirole is an agonist of dopamine, meaning that it can undergo the same mechanism as dopamine. As such, it can act as a neurotransmitter in dopamine's place, alleviating parkinson's.
e) safinamide inhibits the re-uptake of dopamine by the pre-synaptic neuron, so that more dopamine will travel through the synapse and bind to the post-synaptic receptors, alleviating parkinson's.
2. a) stem cell therapy could be used to replace the dopamine-secreting neurons. Stem cells are unspecialised, so they can differentiate to form the missing dopamine-secreting neurons, alleviating parkinson's.
b) gene therapy can be used to insert the gene for producing dopamine-secreting neurons into the cells, alleviating parkinson's.

1. -75mV
2. -30mV, so that any small stimulus would not have a response
3. 10ms and 10ms, 20ms total
4. 100ms
5. 1000/120 = 8.33
6. the start of hyperpolarisation led to a slight initial increase in potential

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1. (a) L-DOPA forms dopamine using the enzyme dopa decarboxylase, which can then be used at synapses in the brain, consequently relieving parkinson's disease since there isn't a lack of dopamine

(b) prevents dopamine from being converted to MAO-B

(c) Inhibits COMT so less tyrosine would be made and more dopamine would be produced

(d) the agonist binds to the dopamine receptor and activates it, which then increase the sensitivity of dopamine

(e) so that the dopamine would only travel to the postsynaptic neurons and bind to the receptors

2. (a) stem cells can differentiate to develop more dopamine secreting neurons

(b) gene alteration to change the base sequence that causes the loss of dopamine secreting neurons

1. -75mV

2. -30mV, it is before the a response that would take place when a stimulus is detected

3. 20ms

4.
5.

6. hyperpolarization starts

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a) L-Dopa is converted to dopamine via dopa decarbobxylase which replaces the lack of dopamine
b) selegeline inhibits MAO-B which is the enzyme which breaks down dopamine, hence the dopamine lasts longer
c)tolcapone inhibits the enzyme which breaksdown L-DOPA into another compound that is not dopamine, hence more dopamine can be formed from L-DOPA
d) the agonist binds and activates the dopamine receptor which increases the senstivity to dopamine
e) When the reuptake of dopamine back into the pre-synaptic neurone is inhibited, the dopamine remains in the synapse longer and can bind to the post-synaptic neurone
2) stem cells can be programmed to replace the lost dopamine secreting neurones. The stem cells can be injected into the region and with epigenetic chemicals which help them specialise into the specific dopamine secreting neurones. This will help secrete more dopamine which will offset the effects of pakinsons.
b) Genes that code for the production or specialisation of cells into dopamine producing neurones can be injected into the patients gene, which can be transcribed by the patients own cells to produce and replace dopamine producing neurones.
1) -75mV
2) -30mV, it is the potential of the neurone just before the sharp rise during the depolarisation
3) 20ms
4)85ms, the estimated time of reaching resting potential is 120ms, the end of the depolarisation is at 35ms. 120ms- 35ms=85ms
5) the total time taken for one action potential starting from the start of the threshold potential is 100ms therefore 1000ms/100ms= 10 action potentials
6) hyperpolarisation