Parkinson's disease - mechanisms

Question 1

What causes Parkinson’s disease? and how? (in genetic cases)

Answer 1

PD is caused by degeneration of dopaminergic axons (death of cell bodies). In genetic cases this is caused by a failure in proteostasis and/or mitochondrial function in the dopaminergic neurons.

Question 2

What neurons are affected in PD?

Answer 2

The dopaminergic neurons that project from the midbrain substantia nigra into the dorsal striatum

Question 3

What causes Parkinson’s disease? and how? (in non-genetic cases)

Answer 3

PD is caused by degeneration of dopaminergic axons (death of cell bodies). The cause of it is still unknown.
It is thought to start either in the nose or gut.

Question 4

How does the pathology of PD start and progress?

Answer 4

It is thought to start either in the nose or gut with accumulation of α-synuclein that travels to the brain, where it makes Lewy bodies, and these somehow affect only the dopaminergic neurons.
The neurons will start to retract their axons and eventually die

Question 5

What is the issue with GDNF-injection treatments in PD?

Answer 5

The neurons start to grow towards the injection site, because they grow towards the neurotrophic factor.
Endogenous upregulation of GDNF may be a better option (enhance levels of GDNF where it is normally found)