Autonomously spiking dopaminergic neurons of the substantia nigra pars compacta (SNpc) are exquisitely specialized and suffer toxic iron-loading in Parkinson's disease (PD). However, the molecular mechanism involved remains unclear and critical to decipher for designing new PD therapeutics. The long-lasting (L-type) Ca_V1.3 voltage-gated calcium channel is expressed at high levels amongst nigral neurons of the SNpc, and due to its role in calcium and iron influx, could play a role in the pathogenesis of PD. Neuronal iron uptake via this route could be unregulated under the pathological setting of PD and potentiate cellular stress due to its redox activity. This Commentary will focus on the role of the Ca_V1.3 channels in calcium and iron uptake in the context of pharmacological targeting. Prospectively, the audacious use of artificial intelligence to design innovative Ca_V1.3 channel inhibitors could lead to breakthrough pharmaceuticals that attenuate calcium and iron entry to ameliorate PD pathology.

黑质致密部 (SNpc) 的自主尖峰多巴胺能神经元非常特化，并在帕金森病 (PD) 中承受有毒的铁负荷。然而，所涉及的分子机制仍不清楚，对于破译设计新的 PD 疗法至关重要。持久（L 型）Ca _V 1.3 电压门控钙通道在 SNpc 的黑质神经元中高水平表达，并且由于其在钙和铁内流中的作用，可能在 PD 的发病机制中发挥作用。通过这种途径的神经元铁摄取在 PD 的病理环境下可能不受调节，并由于其氧化还原活性而增强细胞应激。本评论将重点介绍 Ca _V的作用1.3 药理靶向背景下钙和铁摄取的通道。前瞻性地，大胆使用人工智能来设计创新的 Ca _V 1.3 通道抑制剂可能会导致突破性的药物，减弱钙和铁的进入以改善 PD 病理。