Neurodegenerative Diseases Part 2: Parkinson's
For Neurodegenerative Diseases Part 1: Alzheimer’s, click here.
Parkinson's is a neurodegenerative disorder with very interesting pathophysiology. At the most basic level, Parkinson's symptoms are caused by accumulation of misfolded alpha-synuclein protein, which kills brain cells. These neurons are mainly located in the substantia nigra, which is a cluster of dopamine-secreting neurons in the midbrain of the brainstem. Here's what that looks like:
The alpha-synuclein clusters combine with ubiquitin and clump into Lewy bodies (an example of an inclusion), which are visible under a microscope using immunohistochemistry (basically using antibodies with affinity for Lewy bodies to mark and highlight them under a microscope). Here's what Lewy bodies look like:
Interestingly, Parkinson's isn't the only Lewy-associated neurodegenerative disorder. Lewy body dementia is similar to Parkinson's, except the Lewy bodies cause cell death in the cerebral cortex, limbic cortex, and hippocampus instead of the substantia nigra. The impact on these different regions causes different symptoms. For Parkinson's, the cytotoxic (cell-killing) effects of alpha-synuclein Lewy bodies on dopaminergic neurons cause specific symptoms. The most intuitive symptom of Parkinson's is depression, due to lack of dopamine. However, the lack of dopamine causes other symptoms, as dopamine has secondary functions external to motivation/mood regulation. Lack of dopamine means these secondary functions cannot be served, causing symptoms like hand tremors, stiff/slow movement, and soft/slurred speech, among others.
The stuff I've said so far has been relatively well-established. But here are a few areas that are iffy / still being researched. For example, scientists are considering that the Lewy bodies may not be the cytotoxic agents, instead serving as a way to trap free alpha-synuclein which is what actually exerts cytotoxic effects. We're not sure about this idea yet though.
An interesting idea that contrasts with this free vs. Lewy-bound alpha-synuclein concept relates to the interactions of the immune system with neurons in Parkinson's. Both forms of alpha-synuclein, free and bound, can bind and activate microglia, which interact with astrocytes (neuron support cells) and make the astrocytes kill neurons instead of protecting them. This exacerbates neuron death in Parkinson's, worsening symptoms.
So yeah. That was a bunch of info about Parkinson's that's kinda relevant to USABO. Here's some more cool stuff:
Wiki slay: https://en.wikipedia.org/wiki/Parkinson%27s_disease#Pathophysiology.
More about Parkinson's from a medical, not pathophysiology, perspective: https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes/syc-20376055.
Fun fact: alpha-synuclein, when not misfolded, functions in controlling dopamine release by regulating SNAREs. Here's a nice video about that: https://www.youtube.com/watch?v=FIIK2Gp5WzU.
More on Lewy Body Dementia: https://www.ninds.nih.gov/health-information/disorders/lewy-body-dementia.
