16 - Autophagy II Flashcards
What kind of process is autophagy?
A housekeeping process.
What happens to autophagy overtime?
The efficacy decreases.
What does neuronal specific autophagy disruption in mice cause?
Accumulation of ubiquitin aggregates.
What causes Huntington’s disease?
- A polyglutamine (PolyQ) expansion in the Huntington protein.
- Any more than 35 Q repeats causes Huntington’s.
What comes along with the misfolding and aggregation of PolyQ Huntington?
Ubiquitination and proteosomal degradation.
What happens where there is too much accumulation of ubiquitinated PolyQ Huntington?
This results in aggresome formation and the aggresomes are then targeted for autophagic degradation.
How does Parkinson’s disease develop?
As a result of the loss of dopaminergic neurons.
What is the main neuropathology of Parkinson’s disease?
Aggregates of alpha-synuclein or Lewy Bodies.
How is alpha-synuclein normally degraded?
By chaperone mediated autophagy.
What happens when alpha-synuclein mutates?
The mutated versions block the CMA pathway causing toxicity
What other damaged organelle accumulates in Parkinson’s?
Mitochondria
Why might the accumulation of damaged mitochondria cause parkinsons?
It causes reactive oxygen species (ROS) which damages cellular components so some cases of Parkinson’s might be cause by mitochondria derived oxidative damage.
What 2 enzymes regulate mitophagy?
PARKIN and PINK1
What is autophagy’s role in cancer?
Its tumour supressive
What is the main cause of cancer?
An accumulation of DNA damage.
