Calcium channels and iron metabolism: A redox catastrophe in Parkinson's disease and an innovative path to novel therapies?

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) CaV1.3 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 CaV1.3 channels in calcium and iron uptake in the context of pharmacological targeting. Prospectively, the audacious use of artificial intelligence to design innovative CaV1.3 channel inhibitors could lead to breakthrough pharmaceuticals that attenuate calcium and iron entry to ameliorate PD pathology.

• Publication year

  2021

• Venue

  Redox Biology

• Publication date

  2021-09-15

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.redox.2021.102136PMID 34653841PMCID 8517601
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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