Alzheimers & Huntingtons (General) Flashcards
What Protein Misfolds in Alzheimer’s Disease
Beta-amyloid
Tau
What Protein Misfolds in Huntington’s Disease
Huntingtin
What Amyloid Deposit forms in Alzheimer’s
Beta-amyloid
–> Amyloid Plagues (Extracellular)
Tau
–> Neurofibrillary Tangles (Intracellular)
What Amyloid Deposit forms in Huntingtons
Inclusion Bodies
Huntington’s (What kind of disorder)
Inherited Autosomal Dominant Disorder
Progressive Brain Degradation
Huntington’s (What does it cause)
Progressive Brain Degradation which causes Dementia and Severe Motor Symptoms
- Rapid/Jerky Involuntary Movement
- Especially in the face, fingers, tongue
Huntington’s vs Parkinson’s
Syndome mirrors / is the opposite of Parkinson’s
What encodes the Huntington Protein?
The Huntington Gene encodes the Huntington Protein
Huntington’s Disease (N-Terminal)
Huntington Proteins affected by Huntington’s Disease have an increased number of glutamine residues on N-Terminal
Huntington’s Disease (Residues affect on Neurons)
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
Huntington’s Disease (Effects of Neuron Loss)
Loss of GABAergic neurons results in loss of GABA-mediated inhibition in basal ganglia
–> Results in Hyperactivity of Dopaminergic Neurons
Tetrabenazine Mechanism of Action
Inhibits vesicular monoamine transportation
–> Reduces Dopamine Storage and Release –> Decrease Dopamine
Treats Huntington’s Disease
Chlorpromazine Mechanism of Action
Dopamine Receptor Antagonist
–> Decreases binding to Dopamine Receptor
–> Decrease Dopamine Activity
Treats Huntington’s Disease
Baclofen Mechanism of Action
GABA(B) Receptor Agonist
Lowers neuronal activity
–> Decrease Dopamine
Alzheimer’s (What does it cause)
Dementia (Progressive loss of cognitive function)
Alzheimer’s (Preceding cause)
No preceding cause such as stroke, brain trauma, alcohol
Alzheimer’s (Pathological Features)
Loss of neurons in hippocampus and frontal cortex
The loss of cholinergic neurons is a basis for cognitive deficit and short term memory loss
Alzheimer’s (What causes loss of neurons)
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
Alzheimer’s (What does neuron death cause)
Brain shrinkage
Cholinesterase (What it is?)
Breaks down ACh
Cholinesterase (Different Types?)
Acetylcholinesterase (AChE): Cholinergic Synapse
Butyrylcholinesterase: Plasma
Donepezil / Rivastigmine
- Mechanism
- Location of Action
Cholinesterase Inhibitors
–> CNS AChE selective
–> Will cross BBB and eliminate AChE in the brain
Prevents breakdown of ACh
–> Enhance cholinergic neurotransmission/function
Galantamine / Tacrine
- Mechanism
- Location of Action
Cholinesterase Inhibitors
–> Eliminates AChE in neuromuscular junctions
–> Prevents neuromuscular block
Memantine Mechanism of Action
Blocks NMDA Receptor Ion Channels
Can inhibit excitotoxicity
(Prevents excitation –> prevents overexcitation –> Prevents neuron death)
Drugs that treat Alzheimer (Limitations)
Improve symptoms of disease
Does not inhibit:
Neurodegeneration/disease progression