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bioRxiv · 10.1101/2023.05.27.542565

Low-dose carbon monoxide therapy is neuroprotective in rodent models of Parkinson's disease

Rose, K. N.·Zorlu, M.·Xue, X.·Cai, W.·Lin, S.·Schwarzschild, M.·Chen, X.·Gomperts, S. N.
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Abstract

Paradoxically, cigarette smoking is associated with a reduced risk of Parkinsons disease (PD). This led us to hypothesize that carbon monoxide (CO) levels, which are constitutively but modestly elevated in smokers, might contribute to neuroprotection. Using rodent models of PD based on -synuclein (Syn) accumulation and oxidative stress, we show that low-dose CO mitigates neurodegeneration and reduces Syn pathology. Oral CO administration activated signaling cascades mediated by heme oxygenase-1 (HO-1), which have been implicated in limiting oxidative stress, and in promoting Syn degradation, thereby conferring neuroprotection. Consistent with a neuroprotective effect of smoking, HO-1 levels in cerebrospinal fluid were higher in human smokers compared to nonsmokers. Moreover, in PD brain samples, HO-1 levels were higher in neurons without Syn pathology. Thus, CO in rodent PD models reduces pathology and increases oxidative stress responses, phenocopying possible protective effects of smoking evident in PD patients. These data highlight the potential for low-dose CO modulated pathways to slow symptom onset and limit pathology in PD patients.

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Rose, K. N., Zorlu, M., Xue, X., Cai, W., Lin, S., Schwarzschild, M., Chen, X., Gomperts, S. N.. 2023-05-30. Low-dose carbon monoxide therapy is neuroprotective in rodent models of Parkinson's disease. https://doi.org/10.1101/2023.05.27.542565

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