Pathophysiology explains how and why symptoms appear, by looking at what’s going wrong inside the body.

Understanding pathophysiology helps guide medication and treatment choices as well as early detection of Parkinson’s.

What is pathophysiology?

Pathophysiology refers to the functional changes in the body that occur as a result of a disease. It explains how and why symptoms appear, by looking at what’s going wrong inside the body, not just what the disease looks like from the outside.

The pathophysiology of Parkinson’s primarily involves the degeneration, or slow loss of neurons, in a region of the midbrain called the substantia nigra. These neurons produce dopamine, a neurotransmitter crucial for regulating mood, movement and coordination. As these neurons die, they can no longer produce enough dopamine to send messages and cause symptoms like changes in mood, tremors, rigidity, and slowness of movement. Additionally, the presence of Lewy bodies and abnormal aggregates, or clumps, of the protein alpha-synuclein is a pathological feature of Parkinson’s.

What’s happening in the brain?

At the heart of Parkinson’s is the gradual loss of brain cells (neurons) in a part of the midbrain called the substantia nigra. These cells produce dopamine, a chemical messenger that helps coordinate smooth, purposeful movement.

As these dopamine-producing cells die, the brain struggles to send clear signals to the muscles. This leads to the classic motor symptoms of Parkinson’s, including:

  • Tremor (shaking)
  • Rigidity (muscle stiffness)
  • Bradykinesia (slowness of movement)
  • Postural instability (balance problems)

Dopamine also plays a role in mood, motivation, and sleep—so its loss can contribute to depression, fatigue, and sleep disturbances.

Another key feature of Parkinson’s is the presence of Lewy bodies, or clumps of a protein called alpha-synuclein that build up inside brain cells. These protein deposits are found not only in the midbrain but also in other parts of the central and peripheral nervous system, including the gut and olfactory system (which affects smell).

This widespread distribution helps explain many non-motor symptoms of Parkinson’s, such as:

Researchers believe these changes may begin in the body before reaching the brain, a theory known as the “body-first” or “brain-first” hypothesis.

Beyond dopamine: other brain chemicals involved

While dopamine is central to Parkinson’s, researchers are also exploring the role of other brain chemicals (neurotransmitters), including:

  • Glutamate
  • Serotonin
  • GABA
  • Noradrenaline
  • Adenosine
  • Acetylcholine

These may help explain symptoms like mood changes, sleep problems, and cognitive difficulties, and could lead to new treatment options in the future.

Why is this important for people living with Parkinson’s?

In Parkinson’s, pathophysiology helps us understand:

  • Which brain cells are affected
  • What chemical messengers are disrupted
  • Why symptoms like tremor, slowness, and rigidity occur
  • How non-motor symptoms like sleep issues, mood changes, and digestion problems arise.

Understanding pathophysiology helps:

  • Clinicians tailor treatments: Knowing which pathways are disrupted guides medication choices (e.g. dopamine replacement).
  • Researchers develop better therapies: Targeting the root causes like oxidative stress or protein misfolding.
  • Carers and advocates understand the full picture: Parkinson’s isn’t just about movement, it affects the whole person, including mood, sleep, digestion, and thinking.
  • Early detection: Recognising early non-motor signs like constipation or loss of smell can lead to earlier diagnosis and intervention.

Key Statistics

  1. Parkinson’s starts with brain cells dying
    In Parkinson’s disease, special brain cells that make a chemical called dopamine slowly die off. These cells live in a part of the brain called the substantia nigra. Dopamine helps control movement, mood, and coordination. When there’s not enough dopamine, people may feel stiff, move slowly, or have tremors [1].
  2. Sticky clumps called Lewy bodies damage the brain
    A protein called alpha-synuclein can clump together in brain cells, forming sticky lumps called Lewy bodies. These clumps stop brain cells from working properly and are a key sign of Parkinson’s [2].
  3. Genes and toxins may play a role
    Some people inherit changes in certain genes that raise their risk of getting Parkinson’s. Others may be affected by things in the environment, like pesticides or pollution. Getting older also increases the risk [3].
  4. Parkinson’s affects more than just movement
    While most people know Parkinson’s causes shaking and slow movement, it can also affect sleep, mood, digestion, and even their sense of smell. These early symptoms can show up years before movement problems begin [2].

How do I access support?

It’s advisable to explore all available pathways to find the support that best suits your individual needs. Look to:

  • getting a GP referral to create a team of health professionals with Parkinson‘s experience
  • your state-based Parkinson’s organisation for advice on local services to access
  • private health to see what is covered in relation to consultations and expenses
  • DVA, NDIS or My Aged Care plan supports.

Infosheet under review

References

  • Macphee, G. J. A., & Stewart, D. A. (2006). Parkinson’s disease. Reviews in Clinical Gerontology, 16(1), 1–21. https://doi.org/10.1017/S0959259806002073
  • Sayyaed, A., Saraswat, N., Vyawahare, N., & Kulkarni, A. (2023). A detailed review of pathophysiology, epidemiology, cellular and molecular pathways involved in the development and prognosis of Parkinson’s disease with insights into screening models. Bulletin of the National Research Centre, 47, Article 70. https://doi.org/10.1186/s42269-023-01047-4
  • MacMahon Copas, A. N., McComish, S. F., Fletcher, J. M., & Caldwell, M. A. (2021). The pathogenesis of Parkinson’s disease: A complex interplay between astrocytes, microglia, and T lymphocytes? Frontiers in Neurology, 12, 666737. https://doi.org/10.3389/fneur.2021.666737
Happy middle aged man with neat white beard and glasses looking at a laptop

Donations

Your donation helps us to achieve our core business, to improve the lives of people affected by Parkinson’s in Australia through national advocacy, raising awareness and connecting people living with Parkinson’s, their families and carers, researchers and health professionals in the Parkinson’s community.