Table 1 Examples of environmental factors and their biologic correlates

Smoking

• Nicotine acts at nicotinic acetylcholine receptors to trigger downstream effects that reduce neuronal damage [30]

Physical activity

• Increases serum urate [31]

• Increases neurotrophic factors [32]

Urate

• Anti-oxidant by activating of Nrf2/antioxidant response pathway [33]

Ibuprofen

• Anti-inflammatory effect by activation of peroxisome proliferator-activated receptor gamma (PPARγ) [34]

Calcium channel blockers

• Plausible blockage of calcium-channel induced metabolic stress of mitochondria of DA neurons [35]

Caffeine

• Adenosine A_2A receptor blockade [36]

 Pesticides

• Mitochondrial toxins, oxidative stress [27, 28]

 Dairy

• Urate-lowering effects of dairy products [37]

 Traumatic brain injury

• Breakdown of blood-brain barrier, brain inflammation, impaired mitochondrial function, increase in glutamate release, α-synuclein accumulation [38]

 Anxiety or depression

• May be prodromal symptom rather than risk factor due to loss of serotonergic neuronal cells in dorsal raphe nucleus in early PD [39]

 Beta-blockers

• Aggravate the loss of norepinephrine neurons in locus coeruleus and deficits in norepinephrine in PD [40]