Bioinorganic Mechanisms in Neurodegenerative Diseases

Bioinorganic chemistry examines the interactions between metal ions and biological molecules, revealing critical insights into the aetiology and progression of neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis. Dysregulation of transition metals—including iron, copper and zinc—as well as alkaline earth metals such as calcium, can promote protein misfolding, aberrant aggregation and oxidative damage. In Parkinson’s disease, for example, elevated levels of loosely bound copper or iron catalyse the generation of reactive oxygen species that accelerate α-synuclein fibrillation. In Alzheimer’s disease, metal coordination to amyloid-β peptides influences both oligomer formation and neurotoxicity. More recently, iron-dependent lipid peroxidation has been identified as a driver of ferroptosis in vulnerable neuronal populations, while copper-dependent cell death pathways (“cuprotosis”) are under active investigation. Metalloproteins such as metallothioneins and ferritin serve as protective buffers but may become overwhelmed in states of chronic metal overload or deficiency. These bioinorganic mechanisms intersect with mitochondrial dysfunction, neuroinflammation and impaired proteostasis to produce the hallmark lesions and clinical deficits of each disorder. Understanding the precise coordination chemistry at protein and membrane interfaces has opened new avenues for diagnostic imaging, the development of metal-targeted chelators and the design of metallopharmaceuticals to restore homeostasis and slow disease progression.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Bioinorganic Mechanisms in Neurodegenerative Diseases publication trend

The graph below shows the total number of articles in bioinorganic mechanisms in neurodegenerative diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Bioinorganic Chemistry: The study of metal ions in living systems and their roles in structure, function and pathology.

α-Synuclein: An intrinsically disordered neuronal protein whose pathological aggregation is central to Parkinson’s disease.

Ferroptosis: A regulated form of neuronal death driven by iron-catalysed lipid peroxidation.

Metallothioneins: Small cysteine-rich proteins that bind and detoxify heavy metals, offering protection against oxidative stress.

Oxidative Stress: Cellular injury resulting from excessive reactive oxygen species relative to antioxidant capacity.

References

1. Investigating the impact of Cu2+ on α-synuclein aggregation: A single-molecule approach. International Journal of Biological Macromolecules (2025).
2. Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson’s Disease. Antioxidants (2023).
3. The Construction and Validation of a Novel Ferroptosis-Related Gene Signature in Parkinson’s Disease. International Journal of Molecular Sciences (2023).