The lung-brain axis: elucidating the mechanisms of pulmonary-driven neurological disorders

The brain and lungs represent two of the most vital organs in the human body. The conceptualization of the lung-brain axis has advanced our understanding of the bidirectional communication between the respiratory and central nervous systems. Accumulating evidence indicates that pulmonary diseases, including chronic obstructive pulmonary disease, asthma, acute respiratory distress syndrome and infections such as bacterial pneumonia, influenza and Coronavirus Disease 2019, along with airborne environmental exposures, constitute significant risk factors for various neurological disorders. The lung-brain axis is primarily mediated by microbial, immune, neural, metabolic and hormonal pathways. These mechanisms contribute to the disruption of blood-brain barrier integrity, the activation of neuroglial cells and the dysfunction of the cerebrovascular system, ultimately causing neuronal injury and diverse neurological conditions. Environmental factors, notably airborne particulate matter and chemical pollutants, further amplify the crosstalk among these mechanisms, extending the neurological risk. Here, we summarize the current knowledge regarding the association between pulmonary dysfunction and the development and progression of neurodegenerative diseases (such as Alzheimer’s disease and Parkinson’s disease), stroke, anxiety/depression, epilepsy, and migraine. Additionally, potential therapeutic strategies targeting the lung–brain axis are discussed to foster further research in this emerging field. Elucidating the complex interactions within the lung–brain axis will not only deepen our understanding of the shared pathophysiological mechanisms but also open novel avenues for the early diagnosis, prevention, and treatment of related neurological diseases.