Parkinson disease

Parkinson’s disease, which is sometimes called Parkinson disease, Parkinson’s, or PD, is a movement disorder where the dopamine-producing neurons in the substantia nigra of the brain undergo degeneration.

Parkinson’s is one of the most common neurological disorders. It’s a progressive, adult-onset disease, and it gets more common with age. Most of the time, there’s no known cause. But in a few cases, there might be a genetic cause, like mutations in the PINK1, parkin, or alpha synuclein genes, and in rare cases, Parkinsonian symptoms may be caused by MPTP, a toxic impurity that can be found in the recreational drug MPPP or desmethylprodine, which is a synthetic opioid.

In other people, one or more risk factors, rather than a single outright cause, might contribute to Parkinson’s, for example pesticide exposure or DNA variants in genes like LRRK2.

No matter what the cause is, Parkinson’s derives from the death of dopamine-producing, or dopaminergic, neurons in the substantia nigra. The name substantia nigra means “black substance,” since it is darker than other brain regions when you look at a slice of the brain on an autopsy.

We usually refer to the substantia nigra as if it’s in a single location, but there are actually two of these regions in the brain, one on each side of the midbrain. The substantia nigra is a part of the basal ganglia, a collection of brain regions that control movement through their connections with the motor cortex.

In Parkinson’s, these darkened areas of substantia nigra gradually disappear. Under a microscope, Lewy bodies, which are eosinophilic, round inclusions made of alpha-synuclein protein are present in the affected substantia nigra neurons before they die. The function of alpha-synuclein is unknown, as well as the significance of Lewy bodies, and they are both found in other diseases like Lewy body dementia and multiple system atrophy.

The substantia nigra actually can be split into two sub-regions.

First, there’s the pars reticulata, which receives signals from another part of the basal ganglia called the striatum, which is a term for the caudate and putamen put together, and relays messages to the thalamus via neurons rich in the neurotransmitter GABA, also known as gamma-aminobutyric acid.