This working paper proposes a framework to better understand Parkinson's Disease through ecological homeostasis, suggesting new research directions.
AbstractParkinson's disease (PD) is conventionally characterised as a progressivedopaminergic neurodegenerative disorder centred on the substantia nigra parscompacta. While this model has generated substantial therapeutic advances, itinadequately accounts for the multisystem nature of PD, including immunedysregulation, iron dyshomeostasis, gut-brain axis disruption, autonomic dysfunction,and oscillatory circuit disruption. This working paper introduces EcologicalHomeostasis (EH) as a systems-level integrative framework through which PD maybe more coherently understood. EH proposes that biological viability depends uponthe maintenance of structural invariance across interacting subsystems throughconstraint-preserving dynamics. Within this lens, PD is reconceptualised not as adisease with a singular causal origin, but as a progressive failure of multi-scalecoherence: a narrowing of the system's viable operating envelope. The frameworkintegrates evidence regarding microglial activation, iron-redox amplification,hepcidin-mediated iron redistribution, neuromelanin release, alpha-synucleinpropagation, and gut barrier dysfunction within a coherent regulatory language. Itdistinguishes carefully between established evidence, moderate associations, andspeculative hypotheses. The paper proposes a formal composite Coherence Indexwith a specific longitudinal study design, offers falsifiable research predictions, anddraws conservative clinical implications. A mathematical appendix providesgrounding in dynamical systems theory. EH does not replace mechanisticneuroscience; it provides an integrative language capable of holding theheterogeneity of PD subtypes within a single conceptual architecture. The goal is notto identify the origin of PD, but to illuminate the dynamics that determine whetherand how coherence is lost, maintained, or partially restored.
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Smith et al. (2026) studied this question.
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