Parkinson's is the second most common neurodegenerative disease after Alzheimer's.
The most visible features of this disease are a slowness of movement,
muscle rigidity and tremors at rest.
There are also many often debilitating non-motor symptoms,
some of which may present before the motor problems.
Parkinson's affects many areas of the nervous system
and different types of neurons.
However, much focus has been placed on neurons in brain regions associated with the overt motor symptoms,
notably a region of the midbrain called the substantia nigra pars compacta.
This region forms part of a major pathway in the brain that's critical for facilitating movements.
In Parkinson's, dopaminergic neurons in the substantia nigra gradually die,
leading to the malfunction of this pathway and the characteristic motor problems.
Drugs that replace or mimic dopamine are often used to treat these modes of deficits
but they grow less effective over time.
Deep brain stimulation may also be used to treat symptoms,
however, no current treatment slows the neurodegeneration.
A distinctive pathology in most cases of Parkinson's is clumps of misfolded proteins within neurons.
Lewy bodies are the most common type.
A characteristic component of these is a misfolded protein called alpha synuclein.
These molecules can form small repeated units called oligomers or longer fibrils.
Mounting evidence indicates that these are toxic to neurons
and play a key role in driving Parkinson's.
Unwanted proteins are normally cleared by the cell's different types of protein degrading machinery.
Some evidence points to these systems being overwhelmed by misfolded alpha synuclein
and this might be a key factor in what kills the neurons.
Parkinson's has also been linked to problems with mitochondria.
Mitochondria provide cells with the energy to perform vital functions
they are highly dynamic and can fuse together
or break up into smaller versions in response to a cell's energy demands.
They can also be transported to areas of a cell that need them the most.
However in Parkinson's these processes can be impaired
and mitochondria are unable to sustain proper neuronal function.
As they become old or damaged, mitochondria are removed and replaced.
Again this recycling is thought to be disrupted in Parkinson's,
leading to the accumulation of damaged or worn out mitochondria.
Another idea is that the cells called glia, surrounding neurons,
may play a role in Parkinson's.
As dopamine neurons are lost,
one particular type of glial cell, called microglia,
is thought to take up the resulting cellular debris,
triggering an immune response.
Once activated they release inflammatory cytokines
which activate neighbouring microglia and another type of glial cell called astrocytes.
Chemicals released by activated microglia and astrocytes have been shown to injure neurons.
It remains unclear which mechanisms drive the disease process in Parkinson's.
What is clear is that with time, more areas of the nervous system develop pathology.
And one emerging idea is that this happens through the transmission of misfolded alpha synuclein
While the multifactorial nature of Parkinson's disease progression
might make it hard to fully understand,
it does provide a number of potential therapeutic targets
for slowing or even halting the neurodegeneration.
For example, enhancing the clearance of abnormal proteins
and blocking their transmission,
improving the function of mitochondria,
and targeting the neuroinflammation
are all currently active areas of research.