Providing resources and ideas for therapies and medical developments for Parkinson's disease:


Inflammation and Parkinson's Disease:

The common form of Parkinson's is idiopathic rather than genetic suggesting that there are root causes. One suggested root cause is neuroinflammation which can be activated by infection, industrial and agricultural toxins, mold toxins, heavy metal toxins like mercury, autoimmunity or brain trauma. Inflammation is the defense response of the body and the method for the immune system to alert and call to action to a marked location to rid the body of a pathogen or repair tissue. The inflammatory response of the human body is typically intended to operate until the pathogen is removed or the tissue is repaired. It is a sustained chronic inflammatory response that will cause harm to the body and some specific forms are associated with Parkinson's disease.

Not all inflammation will promote the development of Parkinson's but specific forms have been found to be closely associated. The old adage from the scholars in the world of statistics is that "correlation does not imply causation". This is especially true for Parkinson's research data where detailed study is required to find the scientific principles upon which causation can be inferred. Such is the case of research by Gordon and associates on "Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice". They show that α-synuclein aggregates promote inflammasome activation in brain microglia. The thesis presumes that Parkinson's begins with α-synuclein aggregates rather than what causes their formation. Did they ignore that toxins or other inflammatory agents cause inflammasome activation which cause lysosomal dysfunction leading to the formation of α-synuclein aggregates? Its a chicken and egg problem and its not that simple but it does appear that it could be cyclical.

A few inflammation pathways associated with Parkinson's disease and anti-inflammatory agents are discussed below:


Homocysteine (Hcy) is a general marker for inflammation typically associated with cardiovascular disease. Recent studies have shown a correlation between elevated homocysteine levels in one's blood and Parkinson's disease and is believed to enhance the neuronal susceptibility to various neurotoxic insults. Homocysteine is an amino acid which has been shown to limit the formation of nitric oxide, a basic substance that keeps blood vessels pliable and prevents formation of atherosclerosis. Blood levels of homocysteine can be measured in blood tests and should be between 4 to 15 micro-moles/L. Levels between 15 to 60 micro-moles/L are considered moderately high while levels over 60 micro-moles/L are considered to be severely high. High levels of plasma homocysteine is known as hyperhomocysteinemia and has been attributed to use of levodopa treatments, a deficiency of folate, protein deficiency, sedentary lifestyle and genetic dispositions for low vitamin B6 or B12 (see Parkinson's and genetics: MTHFR C677T and CBS T833C polymorphisms). Other risk factors include smoking, diabetes, arthritis and Crohn's disease. Hyperhomocysteinemia (HHcy) has been associated with several age-related pathologies such as osteoporosis, vascular dementia, Alzheimer’s disease, Parkinson’s disease, cancer, stroke, and cardiovascular disease (CVD).

Treatments for hyperhomocysteinemia include:
  • Vitamin B6 supplementation: B6 facilitates transsulfurated conversion to cysteine
  • Vitamin B12 supplementation: B12 facilitates methylation conversion of homocysteine to methionine
  • folic acid (folate) supplements: Facilitates methylation conversion of homocysteine to methionine
  • eat more beans, fruits and vegetables containing folic acid, beta-carotene and vitamin C
  • Trimethylglycene: 1500 mg per day. Facilitates methylation conversion of homocysteine to methionine. Also increases production of glutathione



The endogenous (produced by the human body) amino acid Glucagon-like peptide-1 (GLP-1) is known for its effect on glucose homeostasis (balanced blood sugar levels and maintaining a proper steady state) and facilitation of insulin signalling and has been targeted for the treatment of type 2 diabetes. GLP-1 receptor activation has shown a positive effect on cellular mitochondrial function and synaptic plasticity and inhibits cell death pathways, reduces neuroinflammation, reduces oxidative stress, and increases neurotransmitter release. The drug "exenatide" was developed to target this receptor and has been approved (FDA approved April 2005) for use to treat 2 diabetes and is hypothesized to restore brain insulin sensitivity leading to its use as a neuroprotective agent in the treatment of Parkinson's disease. The GLP-1 receptors (GLP-1R) are expressed in the pancreas (specifically the pancreatic islets, responsible for the metabolism of glucose) and throughout the brain especially concentrated in the frontal cortex, hypothalamus, thalamus, hippocampus, cerebellum, and substantia nigra. More recently the drug NLY01 has been developed and is in trials for the treatment of Parkinson's.

Also see Drugs in trials targeting the GLP-1 inflamation pathway



Inflammasomes are protein complexes that initiate inflammatory responses and are found at elevated levels in the brains of Parkinson's patients. One specific inflammasome in the brain, NLRP3, is involved in perpetuating chronic inflammation and damaging or even killing brain cells.

Nucleotide-binding domain, Leucine-Rich-containing family, Pyrin domain-containing-3 (NLRP3) is a sensor protein in macrophage immune cells which react to stress and generate "inflammasome" which in turn contains a receptor protein (ASC) that encourages activities (autoinflammatory and autoimmune conditions) which lead to neuron pyroptosis (cell death). Research has shown that fibrillar alpha synuclein, oxidative stress and mitochondrial dysfunction can act as an inflammation trigger for the release of NLRP3 inflammasome. NLRP3 can be activated by a wide array of agents including viruses, bacteria, bacterial toxins, inorganic particles (eg asbestos) and crystallized molecules (eg cholesterol crystals/atherosclerosis, urate crystals/gout). Small molecule drugs targeting NLRP3 inhibition are now in development for Parkinson's disease. For more on NLRP3 see Brain on Fire.

Video prepared by the University at Bonn explaining NLRP3 inflammation.

Also see:



Parkinson’s disease disrupts the production of dopamine neurons and progressively causes the loss of motor control. The orphan nuclear receptor protein Nurr1, a regulator of neurotrophic factor signalling, is essential for development and maintenance of dopamine neurons and has been found to be a potential drug target to treat Parkinson's. Also, rare mutations in Nurr1 are associated with familial Parkinson's disease. Research performed by Professor Kwang-Soo Kim from McLean Hospital and Harvard Medical School in the US and Associate Professor Yoon Ho Sup from Singapore's Nanyang Technological University (NTU Singapore) have found that by activating Nurr1, that it promotes mid-brain dopamine neurogenesis as well as neuroprotective and/or neurorestorative effects and helped ameliorate motor behavior deficits (but not those with dyskinesia-like side effects) in a Parkinson's disease (MPTP induced) animal study.

Another study showed that Nurr1 plays critical roles in both microglia and astrocytes to inhibit proinflammatory genes and protects midbrain dopamine neurons from inflammation-induced death.

Yet another study found that overexpression of alpha-synuclein negatively regulates Nurr1.

Three existing FDA approved drugs were found to activate Nurr1:
  • Chloroquine: anti-malaria
  • Amodiaquine: anti-malaria (no longer used as malaria became resistant)
  • Glafenine: pain relief drug. Showed weaker activity than Chloroquine or Amodiaquine.
All three compounds share an identical chemical scaffold, 4-amino-7-chloroquinoline.



Nuclear factor-kappaB, (NF)‐κB, has been shown to be an important regulator of inflammation which participates in the loss of dopaminergic neurons. (NEMO)‐binding domain (NBD) peptide can inhibit the activation of NF-kB and partially protect protect dopaminergic neurons in the nigra, restore the level of dopamine in the striatum, normalize neurotransmitters and restore locomotor activities.


Activation of Immune System and COX-2:

The brain and central nervous system have a dedicated immune system which lies within the blood-brain-barrier. The immune cells are specialized and called glial cells. Imaging with positron emission tomography (PET) scans of patients with early stage Parkinson's disease showed significantly increased microglial (brain and central nervous system immune cells) activation. The presence of microglial activation has been associated with progressive neuronal dysfunction. One study found that COX-2 inhibition has been shown to reduce neuroinflammation and neurodegeneration in animal models of Parkinson's disease. This was done with a 200 mg/day dose of celecoxib for one month.

Inflammation creative commons

  • Treatments targeting the inflammation pathways of Parkinson's have been shown to be effective.

  • Treating inflammation pathways may not be treating the root cause of the inflammation which may be a toxin or other environmental inflammation agents.