Penetrance and the limits of single-gene explanations

From 18th century London to the promise of a global cure: the 200-year history of Parkinson's disease.

To mark the release of our 'Ask the MD' conversation with The Michael J. Fox Foundation for Parkinson's Research, and to welcome a new influx of listeners, we're sharing one of our very first episodes, first aired in August 2024.

Watch our full 'Ask the MD' interview, focused on lifestyle strategies for boosting brain health, on the foundation's website: https://www.michaeljfox.org/news/lifestyle-strategies-boost-brain-health-ask-md-video

Parkinson's, a neurodegenerative disorder most commonly characterized by tremors and other motor symptoms, is so complex, many medical professionals are starting to classify it as a group of diseases, rather than a single disease.

In this episode, we explain those complexities, including:

• The motor symptoms (e.g. cogwheel rigidity, bradykinesia) and non-motor symptoms (e.g. depression, sleep disorders)

• How the industrial revolution may have brought about environmental factors which contribute to Parkinson's

• The differences and similarities between Parkinson's and other neurodegenerative diseases, like Alzheimer's

• How Parkinson's manifests in our brains

• Why one nurse was able to detect Parkinson's through smell

• The neurogenetics of Parkinson's, and the ethical quandaries of evolving genetic technology

• Why lifestyle — nutrition, exercise, etc. — is so key to preventing and managing Parkinson's

Joining us for this extensive conversation are three incredible guests:

• Dr. Rachel Dolhun, Senior Vice President of Medical Communications at The Michael J. Fox Foundation for Parkinson's Research

• Dr. Michael Okun, evolutionary biologist, movement disorders specialist, and Director of the Norman Fixel Institute for Neurological Diseases

• Dr. Matthew Farrer, neurogenetics expert and Professor Of Neurology at the University of Florida

'Your Brain On' is hosted by neurologists, scientists, and public health advocates Ayesha and Dean Sherzai.

SUPPORTED BY: the 2026 NEURO World Retreat. A 5-day journey through science, nature, and community, on the California coastline: https://www.neuroworldretreat.com/

'Your Brain On... Parkinson's' • SEASON 6 • EPISODE 4 (SEASON 3 REUPLOAD)

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LINKS

Dr. Rachel Dolhun:

At the Michael J. Fox Foundation: https://www.michaeljfox.org/bio/rachel-dolhun-md-dipablm

'Ask the MD' series: https://www.michaeljfox.org/ask-md

The Michael J. Fox Foundation on YouTube: https://www.youtube.com/@michaeljfoxfoundation/videos

Dr. Michael Okun:

At the University of Florida: https://neurology.ufl.edu/profile/okun-michael/

The book 'Ending Parkinson's Disease': https://endingpd.org/

The Norman Fixel Institute: https://fixel.ufhealth.org/

Dr. Matthew Farrer:

At the University of Florida: https://neurology.ufl.edu/profile/farrer-matthew/

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References:

1. Bloem, B. R., Okun, M. S., & Klein, C. (2021). Parkinson's disease. The Lancet, 397(10291), 2284-2303.

2. Morris, H. R., Spillantini, M. G., Sue, C. M., & Williams-Gray, C. H. (2024). The pathogenesis of Parkinson's disease. The Lancet, 403(10423), 293-304.

3. Dorsey, E., Sherer, T., Okun, M. S., & Bloem, B. R. (2018). The emerging evidence of the Parkinson pandemic. Journal of Parkinson's disease, 8(s1), S3-S8.

4. Dorsey, E. R., Okun, M. S., & Tanner, C. M. (2021). Bad Air and Parkinson Disease—The Fog May Be Lifting. JAMA neurology, 78(7), 793-795.

5. Tsalenchuk, M., Gentleman, S. M., & Marzi, S. J. (2023). Linking environmental risk factors with epigenetic mechanisms in Parkinson's disease. npj Parkinson's Disease, 9(1), 123.

6. Reynoso, A., Torricelli, R., Jacobs, B. M., Shi, J., Aslibekyan, S., Norcliffe‐Kaufmann, L., ... & Heilbron, K. (2024). Gene–Environment Interactions for Parkinson's Disease. Annals of Neurology, 95(4), 677-687.

7. Golsorkhi, M., Sherzai, A., & Dashtipour, K. The Influence of Lifestyle on Parkinson's Disease Management. In Lifestyle Medicine, Fourth Edition (pp. 919-924). CRC Press.

8. Sherzai, A. Z., Tagliati, M., Park, K., Pezeshkian, S., & Sherzai, D. (2016). Micronutrients and risk of Parkinson's disease: a systematic review. Gerontology and geriatric medicine, 2, 2333721416644286.

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