Parkinson's Disease

What is Parkinson's?

Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world, with a prevalence rate of one percent in the population over age of sixty, and is the second most common neurodegenerative disease involving movement disorder. Males are most likely to develop PD and its incidence in Caucasians seems higher than in other races.

The condition is characterized by cognitive impairment, physical tremors, slowness of movement (bradykinesia), instability, muscular rigidity, and other non-motor symptoms. Clumps of protein accumulate within specific nerve cells resulting in their death (apoptosis). These neurons are known as “dopaminergic neurons” because they are responsible for the production of dopamine (DA). DA is a neurotransmitter produced from the dietary amino acid tyrosine and plays significant roles in a variety of motor, cognitive, motivational, and neuroendocrine functions. As these neurons die, dopamine production is lost and message transmission between brain cells and the body breaks down. In addition, Parkinson’s is linked to antioxidant loss, free radical increases and mitochondrial dysfunction.

Pathology

The protein associated with Parkinson’s development is known as protein alpha synuclein. Its function in the brain is relatively unknown. But, it has become of great interest to Parkinson’s researchers because it is a major constituent of the hallmark protein clumps, which are called Lewy bodies.

Parkinson's brainAlthough Parkinson’s has been viewed as a neurodegenerative condition resulting from reduced dopamine production and Lewy bodies in the nerve cells, it is now acknowledged to be caused by multisystem neurodegeneration affecting multiple neurotransmission systems.1, 2

  • Accelerated oligomerization of two different alpha-synuclein mutations is a hallmark of early-onset Parkinson’s. This is the process of changing single molecules (monomers) into chains of similar molecules (oligomers).
  • Parkinson’s pathology has a special emphasis on the degeneration of the cholinergic system which has a role in both large-scale and local brain messaging circuits, with impacts that go well beyond cognition.

PD patients have a build-up in plaque primarily in the substantia nigra pars compacta and locus coeruleus regions in the midbrain. These cells produce the neurotransmitters or biochemicals that help regulate the nervous system and body functions.

The substantia nigra pars compacta region of the brain is involved in a wide range of processes such as emotion, reward processing, habit formation, movement, and learning. This part of the brain is particularly involved in coordinating sequences of motor activity, as would be needed when playing a musical instrument, dancing, or playing sports, as it is the section of the brain most effected by Parkinson’s disease.

Causes and Contributing Factors

Genetic and Epigenetic Factors

Genetic factors. Genetic mutations can cause Parkinson's, including mutations to B-synuclein or the PRKN (parkin) gene (which is involved in mitochondria maintenance),3 or the LRRK2 gene (linked to late-onset Parkinson's),4 which are associated with the most common inherited form of the condition.

Environmental pollution. Epigenetics is the study of how toxins change our gene structure. Researchers first noted in 2002, and have since validated that children and young adults who live in areas with significant air pollution are much more likely to have the hallmarks of Parkinson’s due to epigenetics: twisted protein fibers, deteriorating neurons and amyloid plaque deposits.5 The same is true of industrial-, combustion-, and friction-derived nanoparticles.6

Metabolic Factors

B-synuclein aggregation. Clumping of this protein, forming Lewy bodies within dopaminergic nerve cells resulting in nerve cell death.

Dopamine loss. Researchers believe a loss of the neurotransmitter dopamine, neurological damage, inflammation, and brain cell deterioration are among the primary factors that trigger Parkinson’s development.

Cholinergic circuit dysfunction has been associated with neurodegenerative diseases such as Parkinson’s. These circuits participate in aspects of memory formation, motivational and volitional behaviors.

Mitochondrial dysfunction plays a role in contributing to neurodegeneration. Mitochondria are the cellular energy producers.

Excitotoxicity. Excessive activation of certain neural receptors stimulates a toxic effect that initiates premature cell death.

Misfolded protein. The accumulation of misfolded protein is a defining hallmark for the progression of various neurodegenerative diseases including Parkinson’s.

Enzyme imbalance. Certain related enzymes, called transglutaminases, are capable of catalyzing other reactions important for the cell viability and have been shown to be involved in the molecular mechanisms responsible many neurological conditions.

Oxidative Stress and Inflammation

Inflammation. Parkinson’s is characterized by neuroinflammation, appearing in old age when chronic inflammation in the body compromises the immune system.8, 9

Oxidative stress is a factor10, 11 and may either directly damage cellular molecules to cause passive or "accidental" cell death or affect normal cellular signaling pathways and gene regulation to induce premature cell death.

Exposure to Toxins

Neurotoxins are directly implicated in Parkinson’s. For example, L-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP), an industrial chemical, was discovered to produce acutely PD-like symptoms.12

Heavy metal build-up may alter neurotransmission and lead to neurodegeneration, which can manifest as cognitive problems, movement disorders, and learning and memory dysfunction. These include excess copper, lead, manganese, aluminum, and iron.13, 14, 15, 16, 17

High magnesium levels are also noted in PD patients’ blood and cerebrospinal fluid and are considered a risk factor according to a meta-analysis of seventeen published studies.7

Drugs that have been prescribed for depression, Parkinson’s disease, and loss of bladder control are linked to higher risk of dementia up to twenty years after exposure.

Recreational drugs. Amphetamine-type stimulants, have been associated with the onset of PD,18 although cannabis may have therapeutic benefits. More research is needed.

Diet and Digestion

Dairy product consumption (excluding yogurt) may increase one’s risk of PD independently of calcium intake, particularly in men.19 The association is linked to low serum uric acid levels. In addition, the possible presence of dopaminergic neurotoxins, including pesticides and polychlorinated biphenyls in dairy products may increase the risk of PD.20

Canned foods and BPA contamination. Consumption of canned fruits and vegetables is a strong predictor of PD progression, most likely due to the leakage of Bisphenol A (BPA) used in the inner coating of the cans (and in many plastic products). BPA is a well-established endocrine conductor and an energy balance disruptor.21 The aluminum content of the cans may also be contributing to the association as aluminum is a neurotoxicant.

Microbiota. Dysfunction in the brain-gut microbiota axis which has a role in irritable bowel syndrome, inflammatory bowel disease, depression, and anxiety, also may be important in neurodevelopmental disorders.22

Alcohol consumption. Low to moderate alcohol consumption may exert neuroprotective effects in PD, whereas greater liquor consumption increases the risk of PD and earlier onset.23

Sugary drinks such as soda is associated with PD progression. Diet soda is associated with a faster rate of PD progression possibly due to the consumption of the artificial sweetener, aspartame, which is linked to serotonin and dopamine interference, hyperexcitability, and nerve cell degeneration.24

Fried goods should be avoided as they produce free radicals. In PD they accumulate in the substantia nigra, and in the dopaminergic neurons. This weakens the natural waste removal process in the body.25

Daily Life Factors

Sleep disturbances. Research finds that those who sleepwalk or/and talk in their sleep have a fifty percent chance of developing Parkinson’s or dementia within the decade. A variety of sleep disturbances are common in PD patients including insomnia and REM sleep disorders.

Traumatic brain injury (TBI). Trauma to the head, as evidenced by boxers, football players, people who’ve been in an accident, may slightly increase risk, or may trigger or hasten PD onset. One study looked at more than 350,000 vets, half of whom had some level of TBI. (TBI is identified by loss of consciousness and/or memory loss.) They concluded that mild TBI increases risk fifty-six percent and moderate to severe increases risk by eighty-three percent.

Exercise. Although a sedentary lifestyle contributes to general poor health and neurodegeneration, it (and obesity) are not directly linked to Parkinson's. But exercise therapies appear to be helpful.

Next: Parkinson's Support

Footnotes

Note: additional details about sources of this information are available in our guide to Parkinson's, Natural Parkinson's Care, or upon request.

1. Muller LMTM, Bohnen NI. (2013). Cholinergic Dysfunction in Parkinson's Disease. Curr Neurol Neurosci Rep. Sep;13(9):377.
2. Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, et al. (2003). Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. Mar-Apr; 24(2):197-211.
3. Genetics Home Reference. PRKN gene. Retrieved Jun 27 2019 from https://ghr.nlm.nih.gov/gene/PRKN.
4. Li JQ, Tan L, Yu JT. (2014). The role of the LRRK2 gene in Parkinsonism. Mol Neurodegener. 9:47.
5. Calderon-Garciduenas L, Leray F, Heydarpour P, Torres-Jardon R, Reis J. (2016). Air pollution, a rising environmental risk factor for cognition, neuroinflammation and neurodegeneration: The clinical impact on children and beyond. Rev Neurol (Paris). 2016 Jan;172(1):69-80.
6. Calderon-Garciduenas L, Reynoso-Robles R, Gonzalez-Maciel A. (2019). Combustion and friction-derived nanoparticles and industrial-sourced nanoparticles: The culprit of Alzheimer and Parkinson's diseases. Environ Res. 2019 Jul 5;176:108574.
7. Jin X, Liu MY, Zhang DF, Gao H. Wei MJ. (2018). Elevated circulating magnesium levels in patients with Parkinson's disease: a meta-analysis. Neurospychiatr Dis Treat. Nov 19;14:3159-3158.
8. Boyko AA, Troyanova NI, Kovalenko EI, Sapozhnikov AM. (2017). Similarity and Differences in Inflammation-Related Characteristics of the Peripheral Immune System of Patients with Parkinson's and Alzheimer's Diseases. Int J Mol Sci. Dec 6;18(12).
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11. Peterson LJ, Flood PM. (2012) Oxidative stress and microglial cells in Parkinson's disease. Mediators Inflamm. 2012:401264.
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13. Desai V, Kaler SG. (2008). Role of copper in human neurological disorders. Am J Clin Nutr. Sep; 88(3):855S-8S.
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19. Chen H, O'Reilly E, McCullough ML, Rodriguez C, Schwarzschild MA, Calle EE, et al. (2007). Consumption of dairy products and risk of Parkinson's disease. Am J Epidemiol. May 1; 165(9):998-1006.
20. Chen H, Zhang SM, Hernán MA, Willett WC, Ascherio A. (2002). Diet and Parkinson's disease: a potential role of dairy products in men. Ann Neurol. Dec; 52(6):793-801.
21. Le Corre L, Besnard P, Chagnon MC. (2015). BPA, an energy balance disruptor. Crit Rev Food Sci Nutr. 55(6):769-77.
22. Borre YE, O'Keeffe GW, Clarke G, Stanton C, Dinan TG, et al. (2014). Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med. Sep; 20(9):509-18.
23. Eriksson AK, Lofving S, Callaghan RC, Allebeck P. (2013). Alcohol use disorders and risk of Parkinson's disease: findings from a Swedish national cohort study 1972-2008. BMC Neurol. Dec 5;13:190.
24. Rycerz K, Jaworska-Adamu JE. (2013). Effects of aspartame metabolites on astrocytes and neurons. Folia Neuropathol. 51(1):10-7.
25. Shamoto-Nagai M, Maruyama W, Hashizume Y, Yoshida M, Osawa T, et al. (2007). In parkinsonian substantia nigra, alpha-synuclein is modified by acrolein, a lipid-peroxidation product, and accumulates in the dopamine neurons with inhibition of proteasome activity. J Neural Transm (Vienna). 114(12):1559-67.
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