Alzheimers & Huntingtons (General)

Question 1

What Protein Misfolds in Alzheimer’s Disease

Answer 1

Beta-amyloid

Tau

Question 2

What Protein Misfolds in Huntington’s Disease

Answer 2

Huntingtin

Question 3

What Amyloid Deposit forms in Alzheimer’s

Answer 3

Beta-amyloid
–> Amyloid Plagues (Extracellular)

Tau
–> Neurofibrillary Tangles (Intracellular)

Question 4

What Amyloid Deposit forms in Huntingtons

Answer 4

Inclusion Bodies

Question 5

Huntington’s (What kind of disorder)

Answer 5

Inherited Autosomal Dominant Disorder

Progressive Brain Degradation

Question 6

Huntington’s (What does it cause)

Answer 6

Progressive Brain Degradation which causes Dementia and Severe Motor Symptoms
- Rapid/Jerky Involuntary Movement
- Especially in the face, fingers, tongue

Question 7

Huntington’s vs Parkinson’s

Answer 7

Syndome mirrors / is the opposite of Parkinson’s

Question 8

What encodes the Huntington Protein?

Answer 8

The Huntington Gene encodes the Huntington Protein

Question 9

Huntington’s Disease (N-Terminal)

Answer 9

Huntington Proteins affected by Huntington’s Disease have an increased number of glutamine residues on N-Terminal

Question 10

Huntington’s Disease (Residues affect on Neurons)

Answer 10

The more Glutamine Residues on huntingtin protein the earlier the onset
–> Increased glutamine residues causes formation of protein aggregates (Inclusion Bodies)
–> Inclusion Bodies contribute to neuronal loss of GABAergic neurons in cortex and striatum

Question 11

Huntington’s Disease (Effects of Neuron Loss)

Answer 11

Loss of GABAergic neurons results in loss of GABA-mediated inhibition in basal ganglia
–> Results in Hyperactivity of Dopaminergic Neurons

Question 12

Tetrabenazine Mechanism of Action

Answer 12

Inhibits vesicular monoamine transportation
–> Reduces Dopamine Storage and Release –> Decrease Dopamine

Treats Huntington’s Disease

Question 13

Chlorpromazine Mechanism of Action

Answer 13

Dopamine Receptor Antagonist
–> Decreases binding to Dopamine Receptor
–> Decrease Dopamine Activity

Treats Huntington’s Disease

Question 14

Baclofen Mechanism of Action

Answer 14

GABA(B) Receptor Agonist

Lowers neuronal activity
–> Decrease Dopamine

Question 15

Alzheimer’s (What does it cause)

Answer 15

Dementia (Progressive loss of cognitive function)

Question 16

Alzheimer’s (Preceding cause)

Answer 16

No preceding cause such as stroke, brain trauma, alcohol

Question 17

Alzheimer’s (Pathological Features)

Answer 17

Loss of neurons in hippocampus and frontal cortex

The loss of cholinergic neurons is a basis for cognitive deficit and short term memory loss

Question 18

Alzheimer’s (What causes loss of neurons)

Answer 18

Aggregation of A(beta) and Tau proteins causes neuron loss (Cholinergic Neurons)
–> A(beta) Oligomers directly activate NMDA causing Ca2+ overload
–> Excitotoxicity causing neuronal death

Question 19

Alzheimer’s (What does neuron death cause)

Answer 19

Brain shrinkage

Question 20

Cholinesterase (What it is?)

Answer 20

Breaks down ACh

Question 21

Cholinesterase (Different Types?)

Answer 21

Acetylcholinesterase (AChE): Cholinergic Synapse

Butyrylcholinesterase: Plasma

Question 22

Donepezil / Rivastigmine
- Mechanism
- Location of Action

Answer 22

Cholinesterase Inhibitors
–> CNS AChE selective
–> Will cross BBB and eliminate AChE in the brain

Prevents breakdown of ACh
–> Enhance cholinergic neurotransmission/function

Question 23

Galantamine / Tacrine
- Mechanism
- Location of Action

Answer 23

Cholinesterase Inhibitors
–> Eliminates AChE in neuromuscular junctions
–> Prevents neuromuscular block

Question 24

Memantine Mechanism of Action

Answer 24

Blocks NMDA Receptor Ion Channels
Can inhibit excitotoxicity
(Prevents excitation –> prevents overexcitation –> Prevents neuron death)

Question 25

Drugs that treat Alzheimer (Limitations)

Answer 25

Improve symptoms of disease

Does not inhibit:
Neurodegeneration/disease progression