Op-Ed: What If We’ve Misunderstood Parkinson’s from the Start?

I’ve lived with Parkinson’s disease for 35 years. That’s not a typo. I was diagnosed in my early 20s—before most people know what a neurotransmitter even is. Since then, I’ve been through it all: the medications, the side effects, the surgeries, the slumps. I remember one morning in my twenties—standing in the shower, staring at my toothbrush like it was a riddle. My brain had the intent. My hand didn’t care. That disconnect wasn’t caused by protein aggregates. It was the result of dopamine falling through the floor. These were the days when movement didn’t just feel stiff—it felt broken. Like the instructions were getting lost in translation. I even had deep brain stimulation about 15 years ago. And for a long stretch, I was prescribed the dopamine agonist ReQuip at its maximum dosage—24 mg per day. On that dose, I was virtually symptom-free. It was like flipping the lights back on in a room I forgot had windows. I could move, speak, and function like my old self. But that relief came with a trade-off: the impulse control issues associated with dopamine agonists. I found myself obsessively spending, gambling, and chasing risky behaviors without fully recognizing the consequences. It was the chemical definition of a Faustian bargain—dopamine restored, but not without cost. But it also revealed something profound: if stimulating dopamine alone could temporarily erase nearly every symptom, maybe dopamine dysfunction wasn’t just a downstream effect of disease—it was the primary battleground. That experience strengthened my belief that dopamine isn’t reacting to damage—it’s the first thing to go, and the thing we must protect first.

But through it all, one question has haunted me more than any tremor ever could:

What if we’ve gotten the cause of Parkinson’s backward?

Let me explain.

The prevailing theory in Parkinson’s research is tidy and widely accepted: a protein called alpha-synuclein misfolds, clumps into Lewy bodies, and kills the dopamine-producing neurons in the midbrain. This dopamine loss is what causes the stiffness, slowness, and tremors that define Parkinson’s.

But what if that’s not how it actually works—at least not at first?

In Shaky Times, I wrote about what I called “the invisible ceiling”—that maddening place where you’re doing everything ‘right,’ and the disease still outpaces you. I’d maxed out my meds, followed every instruction, but Parkinson’s still got sneakier. Those setbacks didn’t feel like protein attacks. They felt like chemical crashes—like dopamine slipping away, dragging clarity and control with it.

What if dopamine deficiency isn’t a downstream effect of protein clumping, but the first domino to fall? What if losing dopamine creates the kind of biochemical instability that causes alpha-synuclein to misfold?

I know this might sound radical, but stick with me. Dopamine isn’t just a neurotransmitter—it’s chemically volatile. It’s sensitive to oxidation. When not properly handled inside brain cells, it can generate toxic byproducts that damage mitochondria, DNA, and—you guessed it—proteins.

And proteins like alpha-synuclein don’t exist in a vacuum. They’re influenced by their environment. In a stressed, dopamine-deficient neuron, alpha-synuclein is more likely to fold the wrong way. It’s not hard to imagine: remove the guardrail (dopamine), and the machinery starts breaking down.

This isn’t just theory. There’s early evidence that dopamine interacts directly with alpha-synuclein and can even prevent its aggregation in certain conditions. We also know that brain regions with severe dopamine loss are the same ones where Lewy body pathology is worst.

Here’s the kicker: when I had deep brain stimulation (DBS) surgery 15 years ago, the procedure didn’t target protein aggregates. It didn’t even pretend to. It targeted the dopaminergic circuitry—the faulty signals, the broken rhythms. And it helped. Not perfectly, but profoundly. The fact that DBS improves symptoms without touching alpha-synuclein suggests that dopamine dysfunction may be more central to the disease than we realize.

I’m not dismissing protein research. But I am urging the Parkinson’s research community to broaden the lens. Consider that dopamine isn’t just the first casualty. It might be the spark that starts the fire.

If this is true, it changes how we think about treatment. Maybe we shouldn’t be so hesitant to start dopamine therapy early. Maybe we should be looking harder at mitochondrial health, redox balance, and neurochemical regulation as early interventions.

I’m not a scientist in a lab. I’m a man with Parkinson’s in real time. My brain has lived this disease for three and a half decades. And sometimes, lived experience sees patterns long before the models catch up.

So here’s my challenge to researchers: Test the dopamine-first hypothesis. Don’t wait for the clumps. Listen to the chemical signals that go silent first.

ent too long treating the smoke. It’s time we looked for the fire.

— Richie Pikunis