Neuroprotective Potential of Human Platelet Lysate in Parkinson's Disease: Insights Into Oxidative Stress, Mitochondrial Dysfunction, Cell Death, and Reactive Gliosis in Experimental Models

Parkinson's disease (PD) entails complex pathology, with current treatments managing symptoms but failing to halt neurodegeneration. Preclinical evidence suggests human platelet lysate (HPL) from healthy donors as a neuroprotective candidate due to its rich neurotrophic content, though its potential in PD models remains largely underexplored. In this study, we present substantial experimental findings demonstrating the neuroprotective effects of HPL administration in both rotenone (ROT)-induced in vitro as well as in vivo models of PD. Our findings reveal that freshly prepared HPL from healthy humans, obtained through freeze-thaw cell lysis followed by heat treatment and ultrafiltration, exhibits significant neuroprotective effects. This protection, evidenced by the attenuation of ROT-induced cell death in SH-SY5Y cells, was mediated through the reduction of oxidative stress, mitochondrial dysfunction, calcium dysregulation, and apoptosis. Additionally, in PD rats, intranasal HPL administration at various doses counteracted ROT-induced weight loss, improved motor function, balance, and grip strength, and alleviated anxiety, stress, and depression. Additionally, HPL promoted neuronal regeneration, suppressed astrocytic and microglial activation in the substantia nigra and striatum, enhanced antioxidant enzyme expression (glutathione and catalase), and reduced pro-oxidants (malondialdehyde and nitric oxide). These findings underscore HPL's potential as a promising therapeutic strategy for PD, representing a significant advancement in regenerative medicine.