Nanotechnology-enabled delivery of bioactive compounds for neuroprotection in Parkinson's disease: mechanisms and future directions.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder marked by the progressive loss of dopaminergic neurons in the substantia nigra. Its clinical features include motor symptoms such as tremor, bradykinesia, rigidity, and postural instability. The pathophysiology of PD involves oxidative stress, mitochondrial impairment, neuroinflammation, protein misfolding, and aberrant alpha-synuclein aggregation, which disrupt dopaminergic signaling pathways. Biomarkers such as α-synuclein, DJ-1, neurofilament light chain, and imaging biomarkers such as DAT-SPECT are being studied for early diagnosis, evaluation of disease progression, and therapy monitoring. Although advancements have been made, current options-such as dopamine replacement therapy, deep brain stimulation, and physiotherapy-remain largely symptomatic, carry long-term side effects, and fail to halt disease progression. Nanotechnology advancements have brought a major paradigm shift in the management of PD. Curcumin, Resveratrol, and EGCG are bioactive compounds with antioxidant, anti-inflammatory, and neuroprotective properties. However, their clinical use is limited because of poor bioavailability and stability. Nanocarrier systems such as liposomes, dendrimers, and polymeric nanoparticles improve targeted delivery through the blood-brain barrier. This helps in reducing systemic toxicity and enhancing therapeutic effectiveness. The therapeutic mechanism of these nanoformulations mainly involves free radical scavenging, modulation of mitochondrial function, inhibition of α-synuclein fibril formation, and regulation of cell signal transduction pathways such as Nrf2/ARE and NF-κB. The major challenges include large-scale production, long-term safety assessment, regulatory challenges, and site-specific delivery. Future research is moving toward the convergence of gene therapy, nanomedicine, and precision targeting to develop disease-modifying therapy. This approach aims not only to control symptoms but also to potentially control neurodegeneration in PD.