Parks: Degenerative Diseases Flashcards
(39 cards)
What proteins are deposited in Alzheimer disease to form inclusions?
Abeta
Tau
What happens to proteins when they get old or become misfolded?
they become ubiquinated in the proteasome or they are killed by lysosomes (autophagy)
How do inclusions bodies form?
they form when proteins become unfolded but are resistant to degradation –> they form oligomers and begin to aggregate to form large inclusion bodies
**not getting properly degraded by the proteasome or lysosomes
What are the cellular consequences of protein aggregation and inclusions?
- they elicit a stress reaction from the cell
- directly toxic to the neurons
- some aggregates behave like prions and spread from neuron to neuron
When cells are under stress, what happens?
neurodegeneration –> neuron death
When amyloid proteins become misfolded, they form (blank)
Beta-sheet structures called fibrils
T/F: Amyloidosis can occur in the brain and the heart
True
Two characteristic features of Alzheimer disease
neurofibrillary tangles w/i neuron (leads to plump unhealthy neurons)
amyloid plaques in the interstitial space
Where does Alzheimer’s disease usu begin?
hippocampus (around the temporal lobe)
Where does A-Beta come from?
it is cleaved by secretases from amyloid precursor protein to form a bunch of different forms of Abeta monomers; the monomers form oligomers which aggregate
Amyloid precursor protein is cleaved by secretases to form (blank), which form (blank) that aggregate into plaques and tangles and lead to neuronal damage
Abeta monomers; oligomers
What is tau? How is it involved in Alzheimer’s disease?
a microtubular protein which gets hyper-phosphorylated by a kinase that is turned on by Abeta; this causes it to fall off the microtubules, so they are no longer stable
**microtubules are involved in intracellular trafficking
Tau is a microtubular protein. It gets (blank) by amyloid-Beta, and falls off of the microtubule. It forms (blank) and leads to (blank) microtubules
phosphorylated; neurofibrillary tangles; destabilized
Describe the amyloid cascade hypothesis
increased production or decreased degradation of A-beta
plaque formation
hyperphosphorylation of tau
neurofibrillary tangle formation
synaptic dysfuntion and neuron loss
memory loss and cognitive deficits
What can be used to detect beta-amyloid in the brain nowadays?
PET scan with a radioactive tracer
What biomarkers in the CSF can you use to diagnose Alzheimer’s?
low beta-amyloid 1-42 (being used up in the formation of plaques)
high total tau protein (neurons are lysing and releasing tau)
elevated phosphorylated tau
T/F: The amyloid beta and tau CSF tests are not fully conclusive, because normal elderly individuals have amyloid plaques and tau neurofibrillary tangles, too
true
Signs and symptoms of Parkinson’s disease?
tremor rigidity masked facies stooped posture arms, elbows, wrists, hips, knees slightly flexed shuffling steps
How does Parkinson’s differ from Alzheimer’s?
Parkinson’s is a motor disease, which involves the basal ganglia!
**AD no motor symptoms really
What is happening neurologically in Parkinson’s disease?
cell death of dopaminergic neurons in the SUBSTANTIA NIGRA, which control movement
What is Parkinson’s treated with?
L-DOPA
What comprises the Lewy body like inclusion bodies found in Parkinson’s disease?
alpha-Synuclein
These patients present with dementia (like Alzheimer’s) then they develop Parkinsons
dementia with lewy bodies
What is ALS?
upper and lower motor neuron disease
