From peripheral to central (Neuro)degeneration: Is heart-kidney a new axial paradigm for Parkinson’s disease?

Parkinson’s Disease (PD) is primarily characterized by the accumulation of alpha-synuclein (αSyn) and the loss of dopaminergic neurons (DAn). The most evident repercussions of the disease include sympathetic and parasympathetic dysfunction, decreased dopamine (DA) levels, and impaired voluntary movements. Given the multifactorial nature of PD, it is now recognized that several systemic diseases may predispose individuals to the onset and progression of PD as well as influence its therapeutic outcomes. Recent studies have highlighted that patients with cardiovascular disease (CVD) and chronic kidney disease (CKD) face an increased risk of developing PD, independent of the shared risk factors. Indeed, substantial evidence supports the connections between the brain, heart, and kidneys. Elements such as the dopaminergic system, blood pressure regulation, inflammation, autophagy, oxidative stress, and calcium (Ca2+) signaling are recognized as crucial for the functioning of each organ individually. However, these factors may also significantly impact the overall health of the triad. Understanding the interconnection between the brain, heart, and kidneys would be groundbreaking in enhancing our knowledge about their interactions, enabling prompt interventions in the early stages of the disease. With this perspective, this review analyzes the current understanding of the brain-heart-kidney axis as a potential new paradigm for diagnosing and managing PD.