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dc:titleNeurodegeneration as Ecosystem Failure: A New Paradigm for Prevention and Treatment.
dc:creatorVelikić, Gordana
dc:creatorŠupić, Gordana
dc:creatorMarić, Dušica
dc:creatorPuletić, Miljan
dc:creatorD. Marić, Marija
dc:creatorBarać, Branko
dc:creatorMarić, Dušan
dc:subjectneurodegeneration
dc:subjectsynucleinopathies
dc:subjectstrain competition
dc:subjectdysbiosis
dc:subjectimmune dysfunction
dc:subjectviral reactivation
dc:subjectco-infection
dc:subjectdisease-modifying therapy
dc:subjectregenerative therapy
dc:subjectprecision medicine
dc:descriptionNeurodegenerative diseases are widely viewed as brain-centric disorders defined by neuronal loss and protein aggregation. Yet decades of failed disease-modifying trials and mounting evidence of early peripheral symptoms suggest that this view is incomplete. This perspective review uses α-synucleinopathies as an illustrative example to outline how organ-brain axes, exosomal signaling, and strain competition shape disease trajectory, proposing a new clinical model: precision ecosystem medicine. This paradigm shift conceptualizes neurodegeneration as the late-stage manifestation of systemic ecosystem collapse: a progressive breakdown in inter-organ homeostasis driven by microbial imbalance, immune dysfunction, viral reactivation, co-infections, environmental stressors, and toxicant accumulation, when protective systems become saturated. Misfolded proteins such as α-synuclein act as prion-like mediators of this collapse, with distinct conformational "strains" emerging in different organ environments and may propagate to the brain via exosomes and neural pathways. Analyses suggest that understanding these systemic interactions could reveal new therapeutic windows before significant neurodegeneration occurs. This integrative approach establishes a conceptual foundation for regenerative therapies that address the complexity of neurodegenerative diseases beyond symptom management, offering promising directions for revolutionizing patient care with precise, multi-targeted strategies. Reframing neurodegeneration as a multi-organ, ecosystem-level disorder opens new paths for prevention, prediction, and potentially disease-modifying therapies, laying the theoretical foundation for a field of precision ecosystem medicine.
dc:publisherMultidisciplinary Digital Publishing Institute
dc:date2025
dc:typeinfo:eu-repo/semantics/article
dc:typeinfo:eu-repo/semantics/publishedVersion
dc:identifierhttps://stomatoloskifakultet.rs/nauka/publikacija/866
dc:identifierDOI 10.3390/ijms262211207
dc:identifierISSN 1422-0067
dc:sourceInternational Journal of Molecular Sciences 26(22): 11207
dc:languageen
dc:rightsinfo:eu-repo/semantics/closedAccess
dc:rightsSva prava zadržana