Beyond the Brain: Exploring the multi-organ axes in Parkinson’s disease pathogenesis

Background

Parkinson’s Disease (PD), a complex neurodegenerative disorder, is increasingly recognized as a systemic condition involving multi-organ interactions. Emerging evidence highlights roles of organ-brain axes (lung-, liver-, heart-, muscle-, bone-, and gut-brain) in PD pathogenesis. These axes communicate via neural, circulatory, endocrine, and inflammatory pathways, collectively driving neurodegeneration. For example, lung dysfunction in PD involves respiratory impairment and inflammatory signaling, while gut dysbiosis triggers α-synuclein aggregation via the vagus nerve. Such cross-organ interactions underscore PD’s systemic nature, challenging traditional brain-centric models.

Aim of Review

1. Decipher mechanisms linking peripheral organs (e.g., lung, gut) to PD via shared pathways.2. Explore bidirectional organ-brain interactions (e.g., liver metabolism affecting neurotoxin clearance).3. Propose multi-organ therapeutic strategies targeting integrated signaling networks.Key Scientific Concepts of Review.1. Lung-Brain Axis: Respiratory dysfunction (motor impairment, inflammation) exacerbates neurodegeneration.2. Liver-Brain Axis: Metabolic dysregulation alters neurotoxin clearance; drugs (e.g., levodopa) impact liver function.3. Heart-Brain Axis: Autonomic dysfunction reduces cerebral blood flow; neuroendocrine changes promote α-synuclein pathology.4. Muscle-Brain Axis: Neuromuscular/metabolic disruptions worsen motor symptoms.5. Bone-Brain Axis: Bone-derived hormones (osteocalcin, OCN) and inflammation influence cognition.6. Gut-Brain Axis: Dysbiosis drives α-synuclein misfolding; gut metabolites modulate neuroinflammation.Integrated Mechanisms: Shared pathways (neuroinflammation, oxidative stress) create a regulatory network, suggesting therapies targeting multi-organ crosstalk (e.g., probiotics, anti-inflammatory agents).