You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
The Potential of L-Type Calcium Channels as a Drug Target for Neuroprotective Therapy in Parkinson's Disease
Contributor:
Liss, Birgit;
Striessnig, Jörg
imprint:
Annual Reviews, 2019
Published in:Annual Review of Pharmacology and Toxicology
Language:
English
DOI:
10.1146/annurev-pharmtox-010818-021214
ISSN:
1545-4304;
0362-1642
Origination:
Footnote:
Description:
<jats:p> The motor symptoms of Parkinson's disease (PD) mainly arise from degeneration of dopamine neurons within the substantia nigra. As no disease-modifying PD therapies are available, and side effects limit long-term benefits of current symptomatic therapies, novel treatment approaches are needed. The ongoing phase III clinical study STEADY-PD is investigating the potential of the dihydropyridine isradipine, an L-type Ca<jats:sup>2+</jats:sup> channel (LTCC) blocker, for neuroprotective PD therapy. Here we review the clinical and preclinical rationale for this trial and discuss potential reasons for the ambiguous outcomes of in vivo animal model studies that address PD-protective dihydropyridine effects. We summarize current views about the roles of Cav1.2 and Cav1.3 LTCC isoforms for substantia nigra neuron function, and their high vulnerability to degenerative stressors, and for PD pathophysiology. We discuss different dihydropyridine sensitivities of LTCC isoforms in view of their potential as drug targets for PD neuroprotection, and we conclude by considering how these aspects could guide further drug development. </jats:p>