Neurodegeneration 2 Flashcards
Two main theories of the cause of alzheimers?
Deposition of beta-amyloid protein (amyloid cascade hypothesis) or deposition of phosphorylated tau in the form of helical filaments or tangles
Third theory of cause of alzheimers?
Metal hypothesis
Function of amyloid precursor protein?
Unknown, possibly ion transport and memory
What happens to beta amyloid protein when it is broken down by the cell?
It is acted on by secretases
Which secretases can act on amyloid precursor protein?
alpha or beta
Which secretase acts most commonly on APP?
alpha
Which products are formed if alpha secretase acts on APP?
AICD, p3 (both are harmless)
Difference between alpha and beta secretase pathway?
APP is cut at a different location
How can gamma secretase influence the formation of plaques?
Where the gamma secretase cleaves at the C-terminal end
At which AA position in the C terminal does gamma secretase cleave for beta amyloid aggregates to form?
42
At which AA position in the C terminal does gamma secretase cleave for beta amyloid aggregates to not form?
40
What causes parkinsons?
The loss of dopaminergic neurons in the substantia nigra
Where does the substantia nigra usually innervate to?
Striatum
What happens to striatum innervation from the substantia nigra in parkinsons?
It is lost–> cant control movement in the normal way
Which proteins are involved in parkinsons?
Alpha synuclein (PARK1), Parkin (PARK2), DJ-1 (PARK7), PINK01 (PARK6), LRRK2 (PARK8), UCHL1 (PARK5)
What are aggregates of alpha synuclein called?
Lewy bodies
Are lewy bodies intra or extra cellular?
Intracellular
Where in the brain are the cells containing lewy bodies found?
Substantia nigra
WHat is Creutzfeldt-Jakob disease(CJD)?
Main form of human prion disease
WHich disease results in animal models that replicate symptoms observed in humans?
Prion disease
Characteristics of prion diseases?
long incubation period (10-40yrs), large deposits of prion protein, rapid neuronal loss, gliosis, vacuoles
Why does the prion protein misfold?
As a result of interaction with other misfolded prion proteins–> could by why it is transmissible
Why is there a metal hypothesis regarding neurodegenerative diseases?
The proteins associated with NDs (APP, alpha synuclein, prion protein) are all metal binding proteins
What are the two main families of demyelinating diseases?
Demyelinating diseases and dismyelinating diseases
What is a demyelinating disease?
Myelin on axons is destroyed
Most common demyelinating disease?
Multiple sclerosis
What is a dismyelinating disease?
A disease where myelination doesnt occur normally
Cause of multiple sclerosis?
CNS myelin is selectively destroyed–> axon is still there
Onset of MS?
30-40
Observable symptoms of MS?
Muscle weakness, difficulty moving (ataxia), difficulty speaking or swallowing
