Parkinson’s Disease (PD) is a neurodegenerative disorder affecting dopaminergic neurons in a specific part of the brain called the substantia nigra. This normally manifests itself as a series of motor impairments that begins with a slight tremor and gradually results in the inability to walk and take care of oneself properly.
In PD, a particular protein inside the dopaminergic neurons becomes misfolded; alpha-synuclein. The misfolded alpha-synuclein can aggregate with itself and muck things up. When a lot of alpha-synuclein comes together, it develops into what is called a Lewy Body. These Lewy bodies are large clumps of non-functional aggregated protein that they get in the way of normal cellular functions and induce apoptosis, which is cell death. This cell death is one of the major contributors to the loss of the dopaminergic neurons found in Parkinson’s Disease. But what causes the proteins to misfold in the first place?
The answer is inflammation and oxidative stress. Oxidative stress is caused by free radicals that are formed in the endoplasmic reticulum and mitochondria. This happens normally with age, but in PD it occurs early specifically in the dopaminergic neurons. Certain toxins can induce some of this to occur, and there are genetic predispositions as well. Free radicals are very reactive molecules that can irreversibly bind with proteins and other molecules in the cell. If this occurs in the endoplasmic reticulum, it starts to not function properly and creates misfolded proteins like alpha-synuclein. This can also happen in the mitochondria, which causes it to also not function properly. Mitochondria are essential for cellular function, and this by itself can lead to cell death are PD symptoms.
Glial cells near these dying neurons try to help put by initiating an inflammatory response, such as releasing pro-inflammatory cytokines. Normally, this helps by attacking whatever is causing things to go wrong. However, in this case, this inflammation leads to the production of more free radicals and furthering the damage.
To even further the progression of the disease, it appears that misfolded alpha-synuclein can act as a seed that can be transferred from an affected neuron to a healthy neuron, causing the healthy neuron to start producing misfolded alpha-synuclein as well.
To date, most treatments for PD solely work on the symptoms, usually by adding more dopamine to counteract the loss of those dopaminergic neurons. There is no cure. However, the information scientists have gathered has led to a much further understanding of this debilitating disease. Parkinson’s is a multifactorial disease that involves oxidative stress, inflammation, protein misfolding, and mitochondrial malfunction. There is no one drug that is going to cure Parkinson’s, but just maybe we can find the right combination of treatments to erase the damage that is being done.
Parkinson's Disease – What's going on?
