[Back To] The Future of Parkinson's Disease

Everyone (undoubtedly) remembers Michael J. Fox for his work in the Back to the Future movies.  However I don’t believe his acting career will be what people remember.  His career in acting has been very successful by any standards, especially considering his early retirement due to Parkinson’s Disease.  Mr. Fox’s career could have seen even more great films and awards had he not been sidelined early with a neurodegenerative disease that stripped him of his ability to focus on his work.
Parkinson’s disease isn’t like every other neurodegenerative disease although it does share some similarities.  Parkinson’s does see neurodegeneration leading to non-motor symptoms like cognitive decline, similar to what is seen in Alzheimer’s.  However, what sets Parkinson’s a part, is its combination of motor, and non-motor symptoms that afflict those suffering from the condition.  Another unique aspect of this disease is that it appears to spread throughout the CNS, starting in the lower brain stem and eventually spreading to the midbrain and cortical regions.
Many patients tend to suffer from the non-motor symptoms (depression, sleep disturbance, sensory abnormalities, autonomic dysfunction, and cognitive decline) first, with the motor-symptoms (bradykinesia, rigidity, tremor, and postural instability) having a later onset.  Right now there is a good understanding of what is causing the motor symptoms involved in PD however the non-motor symptom pathology is still not understood at this point in time.  As you can imagine, this makes treating PD a very difficult task.
The pathology causing PD is currently being understood as cellular degeneration resulting from oxidative stress and accumulation of lewy bodies (aggregates of misfolded proteins [primarily α-synuclein]).  Cellular degeneration occurs when misfolded proteins accumulate in the cell, forming large lewy bodies that displace other cellular components and put stress on normal cellular function.  Oxidative stress occurs in cells and causes but also results in misfolded protein aggregation.  This causes a bit of a “chicken and the egg” argument as to what causes initial cellular stress leading to degeneration.  When oxidative stress occurs in cells, mitochondrial function is stressed and less ATP can be produced to support cellular functions.  This leads to cellular degeneration.
Protein misfolding in cells isn’t uncommon however there are “clean-up” services that remove these proteins before they aggregate and cause cell damage.  These “clean-up” components of cells are known as lysosomes and proteasomes.  They clean up damaged and harmful molecules found in cells when tagged by a marker known as ubiquitin.  In PD, a gene known as Parkin (which codes for the production of ubiquitin) is mutated and thus proper tagging of harmful molecules in the cell is inhibited, leading to improper aggregation of misfolded proteins.  The proteins that are misfolded in PD is commonly α-synuclein.  Once a cell dies, α-synuclein can be taken up by neighboring neurons and thus can act as a “seed” for further misfolding and protein aggregation leading to neuronal death.  This process is what sets PD apart from other neurodegenerative diseases because of its ability to spread.
Current research is focusing on a “cocktail” of drugs with the ability to treat PD in patients.  One drug isn’t really able to do the trick because of how multifaceted PD is.  There is hope however for PD because of the new findings and amount of research that is currently occurring thanks to generous donors like the Michael J. Fox Foundation.
The future of PD research appears to be bright and though this disease has caused pain in so many peoples’ lives, there is hope it will come to an end.  Michael J. Fox may never appear in another blockbuster hit again; however his work after his acting career may end up being what people most remember him for in the future.  His foundation has shed light on a deadly disease as well as fund research so that the future can be bright for those with this disease.
Until next time,
Sebastian