The Brain–Gut–Bone Axis in Neurodegenerative Diseases: Insights, Challenges, and Future Prospects

Abstract Neurodegenerative diseases are global health challenges characterized by the progressive degeneration of nerve cells, leading to cognitive and motor impairments. The brain–gut–bone axis, a complex network that modulates multiple physiological systems, has gained increasing attention owing to its profound effects on the occurrence and development of neurodegenerative diseases. No comprehensive review has been conducted to clarify the triangular relationship involving the brain–gut–bone axis and its potential for innovative therapies for neurodegenerative disorders. In light of this, a new perspective is aimed to propose on the interplay between the brain, gut, and bone systems, highlighting the potential of their dynamic communication in neurodegenerative diseases, as they modulate multiple physiological systems, including the nervous, immune, endocrine, and metabolic systems. Therapeutic strategies for maintaining the balance of the axis, including brain health regulation, intestinal microbiota regulation, and improving skeletal health, are also explored. The intricate physiological interactions within the brain–gut–bone axis pose a challenge in the development of effective treatments that can comprehensively target this system. Furthermore, the safety of these treatments requires further evaluation. This review offers a novel insights and strategies for the prevention and treatment of neurodegenerative diseases, which have important implications for clinical practice and patient well‐being.