My wonderful, supportive father-in-law asked me recently, “Have they made any progress on what causes Parkinson’s?” Have they ever! The explosion of research makes this a hopeful time to have PD.
In a nutshell, Parkinson’s is due to a failure of the cell’s garbage disposal system to get rid of toxic proteins called alpha-synuclein.
Wait a minute — aren’t proteins a good thing?
Yes, but to function properly, proteins must fold correctly, and they fold in complex ways. As we age, our cells accumulate damaged or misfolded proteins. When proteins fold incorrectly, the cellular machinery can sometimes repair them. When it cannot, parkin enables cells to discard the damaged proteins.
David Walker, an associate professor of integrative biology and physiology at UCLA’s Molecular Biology Institute, says “If a protein is damaged beyond repair, the cell can recognize that and eliminate the protein before it becomes toxic,” he said. “Think of it like a cellular garbage disposal. Parkin helps to mark damaged proteins for disposal. It’s like parkin places a sticker on the damaged protein that says ‘Degrade Me,’ and then the cell gets rid of this protein. That process seems to decline with age. As we get older, the garbage men in our cells go on strike. Overexpressed parkin seems to tell them to get back to work.”
Whoa! What’s “parkin”? That sounds suspiciously like “parkinson”…?
And what’s “overexpressed”?
Parkin is a gene which in Dr. Walker’s research was found to modulate the aging process.
Wow! Sign me up!
Cool your jets — the research was on fruit flies – no fountain of youth yet. The gene was named “parkin” when a mutation in this gene was found to correlate with early-onset PD. In Dr. Walker’s research, scientists “overexpressed” (increased) normal (unmutated) parkin genes, and those lucky fruit flies got up to 25% longer on their 50-day life span.
Conversely, if the parkin gene is mutated…or the alpha-synuclein gene is mutated…or if there are other factors impairing the function of the macroautophagy system (Cell’s garbage disposal)….or if it’s a full moon over Miami…
Hey! Knock it off!
Hey, back at ya — it’s Parkinson’s so answers are never straightforward. Anyway, if one or more myriad (and still largely unknown) factors occur, the garbage men go on strike and the alpha-synuclein proteins don’t get cleaned up.
Parkinson’s Disease is caused by the aggregation in the form of fibrillar deposits of alpha-synuclein, a protein that is naturally abundant at neuron junctions. These misfolded alpha-synuclein aggregates propagate between neurons. When they invade a new neuron, they are capable of recruiting normal alpha-synuclein and adding it to the deposit. For this reason, many researchers advocate that the alpha-synuclein of the aggregates should be considered as an infectious protein, in other words a prion. Highly toxic, the alpha-synuclein deposits end up by triggering a process of apoptosis, which is medical-ese for “kiss goodbye to your dopamine cells”.
Hmmm….tangled webs of proteins getting in the way of brain cell function…
this kind of sounds like Alzheimer’s Disease…?.
Yep, right you are. There are several neurodegenerative diseases that are associated with accumulation of toxic proteins because “the garbage men are on strike”. In addition to AD and PD, diseases include ALS (Lou Gehrig’s Disease), Huntingdon’s Disease, Lewy Body Dementia, Mad Cow Disease and Creutzfeldt-Jakob Disease. The proteins are different but the problem of garbage proteins piling up is similar.
Since the early 1900s, scientists have known that PD has a very specific signature of “Lewy bodies“, which are basically knots of tangled alpha-synuclein proteins. In the old days, scientists could only find these upon autopsies, but now they can be identified via PET scans. Interestingly, about 50% of Alzheimer’s patients also have Lewy bodies. (These differ from PD patients with Lewy bodies, because they impacts different parts of brains.) Now here’s the real shocker: About 10% of “normal” seniors at death also have “incidental” Lewy bodies. This implies that the tangled proteins is a “normal” part of aging, and lends credence to the theory that PD and other neurodegenerative diseases are accelerated aging.
Hmmm….accelerated aging? Does this mean Laura is wise before her time?
I hope so!