Alpha Synuclein Flashcards
Where in the cell is alpha synuclein mainly located?
In the pre-synapse (but also in the nucleus)
What is the physiological function of alpha synuclein?
It is not completely understood but it is thought to be involved in neurotransmitter release and is thought to associate with synaptic vesicles
Why could one say be a reason why it is hard to study monomeric alpha synuclein and its functions?
Because monomeric alpha synuclein is a highly dynamic protein which changes conformation constantly
There’s several mutations which give rise to familial PD, in what region of the alpha synuclein protein are the mutations located
In the N-terminal lipid binding domain
where in the cell are the majority of alpha synuclein aggregates located?
At the presynapse (>90%)
Is the Lewy body load well correlated with disease severity/neurodegeneration/Parkinsonian disease?
No
Give at least 3 examples of proposed mechanisms of alpha synuclein oligomer toxicity inside the cell
- general cellular toxicity
- compromised cell membrane integrity
- synaptic toxicity
- impairment in cellular degradation
- ER dysfunction
Give at least 2 examples of proposed mechanisms of alpha synuclein oligomer toxicity outside the cell
- induction of neuroinflammation (release of pro-inflammatory and cytotoxic substances) through activated microglia
- Disturbed neuronal signaling
- cell to cell propagation of pathology
What is passive vs active immunization?
Passive - administration of an antibody directed towards the target.
Active- vaccination
What is the significance of “Seeding of CSF-derived α-synuclein aggregates”?
It could be a potential diagnostic method.
In some cases of Parkinson disease amyloid beta has been observed in the PNS/ENS, what hypothesis did this generate
A gut to brain propagation of pathologic amyloid beta via the vagus nerve. It has been shown that dopamine neurons degenerate in a pathologic alpha synuclein gut to brain model of PD
