Neurodegenerative Diseases Flashcards
Parkinsons involves which two main brainregions
SN
VTA
When dopaminergic neurons that stretch from the substantia nigra to the corpus striatum begin to deteriorate, what happens
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.
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?
l-dopa gets cut in periphery and can cause problems .. caribdopa blocks this in the periphery and carbidopa cannot cross BBB. Carbidopa inhibits decarboxylase.
Lines of treatment in parkinsons
increase L dopa
dopamine receptor agonist to mimick dopamine effect
Influence metabolism of dopamine and prevent its breakdown
Dopamine agonist (4)
Bromocriptine
Pergolide
Pramipexole
Ropinrole
MAO-B does what
breaks down dopamine
COMT does what
breaks down dopamine
MAO-B inhibitors
Selegilline, rasagilline
COMT inhibitor
Tolcapone and Entacapone
Drugs targeting MAO-A is used to treat
depression
MAO-A is involved in the metabolism of
norepi
MAO-B is involved in the metabolism of
dopamine
Patients may have drug induced Parkinson’s because there are drugs that block D2 receptors in dopaminergic transmission these drug classes are
neuroleptics and antipsychotics . These drugs inhibit dopamine transmission.
Ach blocking drugs
Benzotropine
Biperiden
Procyclidine
Benzotropine
Biperiden
Procyclidine All these drugs target what
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.
Amantadine
anti viral drug— been shown to inhibit NMDA receptors which can help manage Parkinson’s.
Apomorphine
injected. Increases dopaminergic D2 receptors . Usually used in patients who are experiecning bad problems with Parkinson’s. This drug is highly emetogenic.
This was used to target ameloid plaques but patients were still dementing
Humanized mono-clonal antibodies.
If levels of this protein were present in the neuron of hippocamous then normal aging occured, if in cytoplasm ,, this resulted in Alzheimers disease
REST
Four drugs used as Achesterase inhibitors to treat Alzheimers
Donepezil
Tacrin
Rivastigmin
Galantamine
the idea of these was that if patients were losing neurons in the hippocampus then increase cholinergic transmission
Memantine
blocks NMDA transmission
Rivastigmine is a
Achesterase inhibitor
Physostigmine
Rivastigmine is a derivative of physostigmine which had polar properties so it was manipulated and got Rivastigmine .
Galantamine
Ach cholinesterase inhibitor
Drugs used to manage Parkinson’s talked about in class that stimulate dopaminergic transmission derivatives of a fungus clavicleps purpurea
Pergolide and lisuride –these look like LSD.
D2 stimulator talked about in class
apomorphine –highly emetogenic
Increased level of inflammation is factor in
NDD
Involved in inflammation
NkKb and Nrf2
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?
specialized pro resolving metabolites.
The specialized pro resolving metabolites actively do what ?
Actively bring inflammation down
The molecules in the pro resolving metabolites, we have to get
in food
The proresoliving molecules are
omega 3 such as:
DHA
EPA
we are not able to synthesize these
GardeninA or GardeninB
down inflammation
Lower inflammation results from doing what to nfkb and nrf2
up nfrf2 and down nfkb
Mediterranean diet is rich in
anti-inflammatory molecules
Omega 6 ratio to omega 3 ratio is currently
20:1
More omega 6 vs less omega 3 means
more inflammation
BDNF
neuroinflammation decreases BDNF
BDNF is important in
stimulating growth of neurons
Can adults grow new neurons in the brain
yes, we can through a process called adult neurogenesis
Two elements in the brain where growth of new neurons takes place
Hippocampus and VTA
New neurons in VTA gets transported to
olfactory bulb
One of the first symptoms in Alzheimers may be
a gradual loss of smell
BDNF plays a huge role in
depression
How can increase BDNF?
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.
