Parkinson’s disease, from molecules to patients
A learning pathway in six steps for bachelor’s and master’s students. It follows Parkinson’s disease from the patient to the brain region, the neurons and the molecules, then to the animal models and back to the patient.
Before starting
The pathway assumes a basic knowledge of neurons and proteins. The Parkinson’s disease page gives the clinical background, with references. This pathway is for education; it is not medical advice.
The answers are kept in this browser only and are not sent to GloNeuro. At the end they form a worksheet that can be saved or printed. Other pathways are listed on Learning pathways.
1. The patient
Read the sections on signs and symptoms and on what happens in the brain on the Parkinson’s disease page. The best-known signs concern movement: slowness, stiffness and tremor at rest. Many people also have symptoms that do not concern movement, such as a reduced sense of smell, sleep problems or low mood.
2. The brain region
Open the 3D brain atlas at the chapter on movement. Dopamine-producing neurons of the substantia nigra pars compacta send their fibres to the striatum, part of the basal ganglia; this is the nigrostriatal pathway. Sections through the midbrain can be viewed in the atlas library.
3. The neurons
In the stereology guided experiment, count dopaminergic neurons, stained for tyrosine hydroxylase (TH), in the substantia nigra of a mouse model and of controls. A neuron that stops making TH is no longer stained even if it survives, so a second, independent marker of neurons helps to tell cell loss from a change in TH.
4. The molecules
In most people with Parkinson’s disease, the protein alpha-synuclein builds up in clumps inside neurons, called Lewy bodies and Lewy neurites. Rare inherited forms are caused by changes in single genes, among them the gene for alpha-synuclein. Western blotting measures how much of a protein a tissue contains; immunofluorescence shows where it is and in which cells.
5. The models
Toxins such as 6-OHDA or MPTP kill dopaminergic neurons within days to weeks, while models based on alpha-synuclein reproduce its build-up, often with a smaller and slower loss of neurons. No model reproduces the whole disease, so the model is chosen to suit the question.
6. Back to the patient
Levodopa and other drugs that replace or mimic dopamine relieve the movement symptoms, and deep brain stimulation helps some patients. At the time of writing, no treatment has been shown to slow the progression of the disease; the treatment section of the Parkinson’s disease page gives the current position.
The worksheet
The answers above form the worksheet. It can be saved as a text file in Markdown format or printed. A completed worksheet is a record of the reasoning, not a grade or a certificate.
Notes for supervisors
Suited to a module on neurodegeneration or neuropathology; about three hours, or two sessions with the stereology experiment between them.
Bachelor’s students can focus on steps 1 to 4. Master’s students can be asked to defend the choice of model in step 5 and to design the study in step 6 with a named primary outcome and its measurement.
Discussion points: cause and consequence in a disease that develops over years, what animal models can and cannot show, and the difference between relieving symptoms and slowing a disease.
Last updated