Nanotechnology meets neurodegeneration: restoring lysosomal function with nanovectors

Neurodegenerative diseases (NDs) remain a growing burden worldwide. Characterized primarily by degeneration of neurons in the central nervous system (CNS), driven in part by pathological protein aggregates and by alterations of the autophagy-lysosomal pathway (ALP), current therapeutic strategies only mitigate the outcomes of NDs rather than their origin, highlighting the need for the development of new targeted therapies.

CNS-targeted nanoparticles (NPs) to tackle ALP have offered promising avenues by bypassing biological barriers, reducing pathological protein aggregates, restoring lysosomal pH and activity, upregulating autophagic flux, and contributing to neuroprotection. This report summarizes recent advances in the development of CNS-Targeted nanocarriers for autophagy as a treatment for ND.

Restoring ALP function is a promising disease-modifying strategy for NDs, as it helps clear toxic protein aggregates. Nanotechnology offers an effective way to deliver such therapies to the brain by overcoming the blood-brain barrier, enabling targeted, multimodal, and potentially cell-specific interventions. However, key challenges remain, including late diagnosis, the need for precise cell targeting, and concerns about long-term safety and bioaccumulation. Despite these limitations, growing research interest is expected to accelerate the development and clinical translation of these approaches.