Calcium channels and iron metabolism: A redox catastrophe in Parkinson's disease and an innovative path to novel therapies?
Matthew K. Boag,
Linlin Ma,
George D. Mellick,
Dean L. Pountney,
Yunjiang Feng,
Ronald J. Quinn,
Alan Wee-Chung Liew,
Mahendiran Dharmasivam,
Mahan Gholam Azad,
Rizwana Afroz,
Des R. Richardson
Affiliations
Matthew K. Boag
Centre for Cancer Cell Biology and Drug Discovery, Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia; School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, Queensland, 4215, Australia
Linlin Ma
School of Environment and Science, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia
George D. Mellick
School of Environment and Science, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia
Dean L. Pountney
School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, Queensland, 4215, Australia
Yunjiang Feng
School of Environment and Science, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia
Ronald J. Quinn
Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia
Alan Wee-Chung Liew
School of Information & Communication Technology, Griffith University, Gold Coast, 4215, Australia
Mahendiran Dharmasivam
Centre for Cancer Cell Biology and Drug Discovery, Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia; School of Environment and Science, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia
Mahan Gholam Azad
Centre for Cancer Cell Biology and Drug Discovery, Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia; School of Environment and Science, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia
Rizwana Afroz
Centre for Cancer Cell Biology and Drug Discovery, Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia; School of Environment and Science, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia
Des R. Richardson
Centre for Cancer Cell Biology and Drug Discovery, Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia; School of Environment and Science, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia; Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, 4111, Australia; Corresponding author. Centre for Cancer Cell Biology and Drug Discovery, Griffith University, Brisbane, 4111, Queensland, Australia.
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.
