Neuromelanin and Iron in Parkinson's Disease: Mechanisms, Heterogeneity, Biomarkers, and Progression

Understanding the intricate interplay between neuromelanin and iron in the brain is a rapidly evolving area of Parkinson’s disease (PD) research. Parkinson’s disease is characterized by extensive heterogeneity in both clinical presentation and disease progression, a variability that is only partially explained by traditional pathological markers. Recent advances highlight that neuromelanin, a pigmented polymer in dopaminergic neurons, and brain iron content, particularly within the substantia nigra and related brainstem nuclei, may jointly modulate neurodegeneration and underlie the observed clinical diversity. However, despite mounting evidence linking regional differences in neuromelanin and iron with distinct PD subtypes and trajectories, significant gaps remain in comprehending the mechanisms driving these variations, how they interact at the molecular and network levels, and their implications for precision diagnostics.

This Research Topic aims to clarify the mechanisms through which neuromelanin and iron contribute to Parkinson’s disease heterogeneity. The primary goal is to unite original investigations and authoritative reviews that systematically examine the dynamic relationship between neuromelanin and iron accumulation in PD, employing methodologies ranging from neuroimaging and high-resolution neuropathology to molecular and cellular techniques. Central questions include: How do spatial and temporal changes in neuromelanin and iron deposition characterize clinical subtypes and influence progression rates? Can advances in imaging, biomarker discovery, and computational analysis improve subtype classification and prognostic accuracy? This collection seeks to illuminate the translational potential of these biomarkers in stratifying patients and guiding targeted interventions.

The scope of this Research Topic encompasses both experimental and methodological studies that elucidate the multifaceted roles of neuromelanin and iron in defining PD subtypes and trajectories. It is limited, however, to investigations that directly address the interrelation between these factors within Parkinsonian pathology and exclude broader discussions of non–PD neurodegeneration. To gather further insights into these complex associations, we welcome articles addressing, but not limited to, the following themes:

- Regional mapping of neuromelanin and iron in substantia nigra and brainstem nuclei
- Neuromelanin–iron interactions and their role in clinical and pathological heterogeneity
- Development and integration of neuromelanin-sensitive and iron-sensitive MRI techniques
- Deep learning and advanced imaging analytics for subtyping and progression monitoring
- Correlation of imaging, neuropathology, and molecular findings with clinical outcomes
- Translational implications for prognosis, stratification, and therapy development

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Neuromelanin, iron deposition, Parkinson’s disease, substantia nigra, brainstem nuclei, disease heterogeneity, clinical subtypes, disease progression, neurodegeneration, magnetic resonance imaging, neuromelanin-sensitive MRI, iron-sensitive MRI

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.