Graphene Quantum Dots in Neurodegeneration: Protein Aggregation and the Microglial State as Therapeutic Targets.

Graphene quantum dots (GQDs) constitute the zero-dimensional family of carbon nanomaterials, combining efficient penetration of the blood-brain barrier (BBB) with precisely controllable surface chemistry, and have drawn attention as theragnostic platforms that carry both diagnosis and therapy in a single particle. Although various neurodegenerative diseases each arise from a different causal protein, they converge on shared pathology: aberrant accumulation of neuronal proteins and chronic neuroinflammation driven by pathological activation of glial cells such as microglia and astrocytes. GQDs modulate aggregation through monomer capture that delays nucleation, the blockade of growing fibril tips, and the penetration and disassembly of mature fibrils, all of which have been verified against various protein aggregation models. Beyond aggregation control, heteroatom doping and surface functionalization design allow GQDs to scavenge reactive oxygen species (ROS) and adjust autophagic pathways, attenuating markers of pathological microglial activation. Tunable emission simultaneously enables imaging of pathological burden and high-sensitivity detection of fluid biomarkers, supporting integration of therapeutic and diagnostic functions. GQD bioactivity, however, is inherently double-edged: depending on composition and concentration, the same materials can trigger mitochondrial oxidative stress and ferroptosis rather than exerting antioxidant action, as observed in microglia and macrophages. Therefore, key challenges remain separating anti-inflammatory efficacy from toxicity through precise surface functionalization, ensuring batch-to-batch reproducibility, establishing standardized physicochemical reporting, and quantitatively delineating the therapeutic window.