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Calcium and Parkinson's disease.

D James Surmeier1, Paul T Schumacker2, Jaime D Guzman1

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|September 4, 2016
PubMed
Summary

Dihydropyridines, which block Cav1 calcium channels, may slow Parkinson's disease (PD) progression. A clinical trial is investigating if isradipine can protect dopaminergic neurons and reduce PD symptoms.

Keywords:
DopamineElectrophysiologyEndoplasmic reticulumMitochondriaOxidant stressSubstantia nigraTwo photon microscopy

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Area of Science:

  • Neuroscience
  • Neurodegenerative Diseases
  • Mitochondrial Biology

Background:

  • Parkinson's disease (PD) is the second leading neurodegenerative disorder globally.
  • Dopaminergic neuron loss in the substantia nigra pars compacta (SNc) causes PD motor symptoms.
  • Cav1 calcium channels in SNc neurons contribute to mitochondrial oxidant stress, potentially increasing vulnerability.

Purpose of the Study:

  • To review the rationale for investigating dihydropyridines as a therapeutic strategy for PD.
  • To discuss the potential of targeting Cav1 channels to slow PD progression.
  • To outline unanswered questions regarding this therapeutic approach.

Main Methods:

  • Review of existing literature on PD pathogenesis, mitochondrial function, and Cav1 channel modulation.
  • Analysis of the mechanism linking Cav1 channel activity to oxidative stress and neurodegeneration.
  • Examination of preclinical and clinical evidence for dihydropyridine efficacy in PD.

Main Results:

  • Cav1 channel-mediated calcium entry drives mitochondrial oxidant stress in SNc neurons.
  • This chronic stress may compromise mitochondrial function and increase susceptibility to proteostatic challenges.
  • Dihydropyridines, negative allosteric modulators of Cav1 channels, show potential for reducing PD risk and progression.

Conclusions:

  • Targeting Cav1 channels with dihydropyridines represents a promising therapeutic avenue for Parkinson's disease.
  • Modulating this pathway may mitigate neurodegeneration by reducing basal mitochondrial oxidant stress.
  • Further research and clinical trials, such as the ongoing NIH-sponsored trial of isradipine, are crucial to validate efficacy.