Neurodegenerative Diseases

Question 1

Parkinsons involves which two main brainregions

Answer 1

SN

VTA

Question 2

When dopaminergic neurons that stretch from the substantia nigra to the corpus striatum begin to deteriorate, what happens

Answer 2

the dopamine neurons extending from sub nigra keep a balance between Ach neurons and GABA neurons in the Corpus striatum. When we lose the dopamine neurons, Ach neurons takes over the GABA neurons which causes involuntary movements. It has been thought that we can block cholinergic transmission to regain function.

Question 3

Dopamine cant cross BBB but L dopa can the diff is that L dopa has an additional carboxyl group which can be taken up by amino acid transporter to get into CNS. In brain it gets cut to form dopamine. What is the problem here?

Answer 3

l-dopa gets cut in periphery and can cause problems .. caribdopa blocks this in the periphery and carbidopa cannot cross BBB. Carbidopa inhibits decarboxylase.

Question 4

Lines of treatment in parkinsons

Answer 4

increase L dopa
dopamine receptor agonist to mimick dopamine effect
Influence metabolism of dopamine and prevent its breakdown

Question 5

Dopamine agonist (4)

Answer 5

Bromocriptine
Pergolide
Pramipexole
Ropinrole

Question 6

MAO-B does what

Answer 6

breaks down dopamine

Question 7

COMT does what

Answer 7

breaks down dopamine

Question 8

MAO-B inhibitors

Answer 8

Selegilline, rasagilline

Question 9

COMT inhibitor

Answer 9

Tolcapone and Entacapone

Question 10

Drugs targeting MAO-A is used to treat

Answer 10

depression

Question 11

MAO-A is involved in the metabolism of

Answer 11

norepi

Question 12

MAO-B is involved in the metabolism of

Answer 12

dopamine

Question 13

Patients may have drug induced Parkinson’s because there are drugs that block D2 receptors in dopaminergic transmission these drug classes are

Answer 13

neuroleptics and antipsychotics . These drugs inhibit dopamine transmission.

Question 14

Ach blocking drugs

Answer 14

Benzotropine
Biperiden
Procyclidine

Question 15

Benzotropine
Biperiden
Procyclidine All these drugs target what

Answer 15

Muscarinic recpeptors. They partially block nicotinic but mostly muscarinic

These have lots of side effects becasue they block Ach on the periphery. I,e (saliva) Results from nonspecific binding causing anti cholinergic effects.

Question 16

Amantadine

Answer 16

anti viral drug— been shown to inhibit NMDA receptors which can help manage Parkinson’s.

Question 17

Apomorphine

Answer 17

injected. Increases dopaminergic D2 receptors . Usually used in patients who are experiecning bad problems with Parkinson’s. This drug is highly emetogenic.

Question 18

This was used to target ameloid plaques but patients were still dementing

Answer 18

Humanized mono-clonal antibodies.

Question 19

If levels of this protein were present in the neuron of hippocamous then normal aging occured, if in cytoplasm ,, this resulted in Alzheimers disease

Answer 19

REST

Question 20

Four drugs used as Achesterase inhibitors to treat Alzheimers

Answer 20

Donepezil
Tacrin
Rivastigmin
Galantamine

the idea of these was that if patients were losing neurons in the hippocampus then increase cholinergic transmission

Question 21

Memantine

Answer 21

blocks NMDA transmission

Question 22

Rivastigmine is a

Answer 22

Achesterase inhibitor

Question 23

Physostigmine

Answer 23

Rivastigmine is a derivative of physostigmine which had polar properties so it was manipulated and got Rivastigmine .

Question 24

Galantamine

Answer 24

Ach cholinesterase inhibitor

Question 25

Drugs used to manage Parkinson’s talked about in class that stimulate dopaminergic transmission derivatives of a fungus clavicleps purpurea

Answer 25

Pergolide and lisuride –these look like LSD.

Question 26

D2 stimulator talked about in class

Answer 26

apomorphine –highly emetogenic

Question 27

Increased level of inflammation is factor in

Answer 27

NDD

Question 28

Involved in inflammation

Answer 28

NkKb and Nrf2

Question 29

For many years it was believed that inflammation was a self resolving process, but this is not the way it works. There are molecules that actively inhibit inflammation which are called?

Answer 29

specialized pro resolving metabolites.

Question 30

The specialized pro resolving metabolites actively do what ?

Answer 30

Actively bring inflammation down

Question 31

The molecules in the pro resolving metabolites, we have to get

Answer 31

in food

Question 32

The proresoliving molecules are

Answer 32

omega 3 such as:
DHA
EPA

we are not able to synthesize these

Question 33

GardeninA or GardeninB

Answer 33

down inflammation

Question 34

Lower inflammation results from doing what to nfkb and nrf2

Answer 34

up nfrf2 and down nfkb

Question 35

Mediterranean diet is rich in

Answer 35

anti-inflammatory molecules

Question 36

Omega 6 ratio to omega 3 ratio is currently

Answer 36

20:1

Question 37

More omega 6 vs less omega 3 means

Answer 37

more inflammation

Question 38

BDNF

Answer 38

neuroinflammation decreases BDNF

Question 39

BDNF is important in

Answer 39

stimulating growth of neurons

Question 40

Can adults grow new neurons in the brain

Answer 40

yes, we can through a process called adult neurogenesis

Question 41

Two elements in the brain where growth of new neurons takes place

Answer 41

Hippocampus and VTA

Question 42

New neurons in VTA gets transported to

Answer 42

olfactory bulb

Question 43

One of the first symptoms in Alzheimers may be

Answer 43

a gradual loss of smell

Question 44

BDNF plays a huge role in

Answer 44

depression

Question 45

How can increase BDNF?

Answer 45

Exercise -muscles synthesize myokines which can penetrate BBB to stimulate production of BDNF
Intermittent fasting - ketone bodies can stimulate production of BBB. Body depletes glycogen then it starts burning fat .. fat broken down into glycerol and free fatty acids. Fatty acids under goes beta oxidation giving off ketones . Ketones can be fuel but can also stimulate the synthesis of BDNF. Physical activity is highly suggested in treatment of depression.