Study reveals lung-brain link between smoking and neurodegeneration
· News-Medical"This research establishes a clear 'lung-brain' axis that helps explain why cigarette smoking is linked to cognitive decline and neurodegenerative risks," said UChicago postdoctoral researcher Kui Zhang, co-first author of the new work. "By understanding how these exosomes perturb iron homeostasis, we open new doors for protecting neurons from smoke-induced damage."
Whether this proves to be a causal link for dementia or not, the research itself is a powerful advance in scientists' understanding of the lungs.
From lung to brain
PNECs are unique lung cells that blend the functions of both nerve cells and endocrine cells. Speaking the languages of both synapse and hormone, they are important sensors for the airway, but difficult to study.
"The primary challenge was the extreme rarity of PNECs, which make up less than 1% of lung cells, making them nearly impossible to isolate and study in depth," Zhang said.
When exposed to nicotine, the iPNECs emitted great quantities of exosomes, tiny particles that contain biological material like proteins, lipid or nucleic acids. Most cell types produce exosomes, but the particular exosomes the iPNECs produced in response to nicotine were rich in a protein called serotransferrin, which the body uses to regulate the flow of iron through the bloodstream.
"This nicotine will have an impact on the PNEC, and this PNEC will release a massive amount of exosomes, and that causes perturbation in terms of iron homeostasis," said co-first author Abhimanyu Thakur, who was with UChicago PME and the Ben May Department during the research and is now at Harvard Medical School's Department of Neurosurgery. "We are finding neurodegeneration-related markers, which are going up, and which can be linked with many cognitive and dementia-related diseases."
Work ahead
"This iron dyshomeostasis drives oxidative stress, mitochondrial dysfunction, and increased α-synuclein expression – hallmarks of neurodegenerative disease," Chen said.
An iron imbalance in neurons can also wrongly trigger ferroptosis, a form of programmed cell death, in cells that weren't supposed to die. Previous research has associated ferroptosis with both Alzheimer's and Parkinson's, but much more study is needed before any causal link can be claimed.
The team is next looking to see if blocking the exosomes – the original source of the signal – could have therapeutic applications. While direct impact on humans is still years off, the research advances scientists' understanding of how the brains and lungs communicate.
"Understanding these cross-organ communication pathways is critical for developing better prevention and intervention strategies for neurodegenerative diseases," Chen said.
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