Edaravone

Edaravone is a free radical scavenger with a strong neuroprotective effect that regulates mitochondrial function in different neurodegenerative diseases. Edaravone can reduce the oxidative stress and mitochondrial dysfunction associated with neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Edaravone treatment in vitro was shown to improve mitochondrial membrane potential, decrease ROS production, and inhibit apoptosis in neuronal cells. It prevents Aβ-induced mitochondrial dysfunction in an AD model and restores mitochondrial dynamics in a PD model by regulating the expression of mitochondrial fission and fusion-related proteins. Edaravone was also found to decrease mitochondrial swelling and dysfunction in ex vivo and in vivo studies.

Fig. 1 Edaravone modulates mitochondrial function. (Cha S J, Kim K. 2022)

Ischemic stroke-induced neurological injury is one of the leading causes of long-term disability and death. The effectiveness of currently available neuroprotective agents is not satisfactory, as these small molecule drugs have short circulation half-life and poor BBB permeability. Edaravone (EDA)-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The NG/EDA is triggered by acidic and EDA-induced high-level GSH microenvironments to achieve the selective and sustained drug release at the ischemic injury site. NG/EDA efficiently accumulated at cerebral ischemic injury site of pMCAO mice and demonstrated efficient BBB crossing ability. NG/EDA with 50 µM EDA significantly improved neuron survival (29.3%) after oxygen and glucose deprivation (OGD) by inhibiting ferroptosis. The pH/GSH dual-responsive nanoplatform might provide a unique and promising strategy for neuroprotection in ischemic stroke and other CNS diseases.

Fig. 2 Targeted neuroprotection through inhibiting ferroptosis by NG/EDA in cerebral ischemia injury. (Zhang Y, et al. 2024)