HQ Team
August 29, 2024: Smoking cigarettes may protect humans from neurodegeneration and prevent the accumulation of a key Parkinson’s-associated protein in the brain, new research on mice reveals.
Research conducted by scientists from Massachusetts General Hospital and Harvard Medical School showed that low doses of carbon monoxide were behind the reduced risk of Parkinson’s disease.
“Because smoking has consistently been associated with a reduced risk of Parkinson’s disease, we wondered whether factors in cigarette smoke may confer neuroprotection,” said senior author Stephen Gomperts, an attending physician at Massachusetts General Hospital.
“We considered carbon monoxide in part because it is generated endogenously in response to stress and has been shown to have protective properties at low levels,” said Gomperts, who is also an associate professor of neurology at Harvard Medical School.
In addition, overexpression of heme oxygenase-1, a stress-induced enzyme that produces endogenous carbon monoxide, has been found to protect dopaminergic neurons from neurotoxicity in an animal model of Parkinson’s, he said in a statement published in Harvard Gazette.
Slow the onset
The low doses of carbon monoxide were comparable to that experienced by smokers. Nicotine, a major constituent of cigarette smoke, is ineffective at slowing the disease’s progression as found in a recently reported clinical trial.
“Molecular pathways activated by low-dose carbon monoxide may slow the onset and limit the pathology in Parkinson’s disease,” Gomperts said.
Gomberts and his colleagues administered a low dose of carbon monoxide (comparable to the exposure experienced by people who smoke) in the form of an oral drug product.
They found it protected the rodents against hallmark features of the disease, including the loss of dopaminergic neurons and the accumulation of the Parkinson’s-associated protein alpha-synuclein in neurons.
Activate signalling pathways
Low-dose carbon monoxide activates signalling pathways that limit oxidative stress and degrade alpha-synuclein, a neuronal protein that is linked genetically and neuropathologically to Parkinson’s disease.
The team also found that heme oxygenase-1 was higher in the cerebrospinal fluid of people who smoke compared with nonsmokers.
Haem oxygenase 1 (HO-1), an inducible enzyme responsible for the breakdown of haem, is primarily considered an antioxidant and has long been overlooked by immunologists.
However, research over the past two decades in particular has demonstrated that HO-1 also exhibits numerous anti-inflammatory properties.
In brain tissue samples from patients with Parkinson’s, heme oxygenase-1 levels were higher in neurons that were free of alpha-synuclein pathology.
Trial on humans
“These findings suggest that molecular pathways activated by low-dose carbon monoxide may slow the onset and limit the pathology in Parkinson’s disease.
“They support further investigation into low-dose carbon monoxide and the pathways it modifies to slow disease progression,” said Gomperts.
The scientists plan a clinical trial of low-dose, orally administered carbon monoxide in patients with Parkinson’s disease.
They will build on multiple phase 1 and phase 2 clinical studies in both healthy people and people with a variety of clinical conditions showing the safety of carbon monoxide at the low doses studied in mice.
