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Microglial KCa3.1 Channels as a Potential Therapeutic Target for Alzheimer’s Disease
Joint Authors
Jenkins, David Paul
Jin, Benjamin E.
Wulff, Heike
Maezawa, Izumi
Source
International Journal of Alzheimer's Disease
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-05-22
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
There exists an urgent need for new target discovery to treat Alzheimer’s disease (AD); however, recent clinical trials based on anti-Aβ and anti-inflammatory strategies have yielded disappointing results.
To expedite new drug discovery, we propose reposition targets which have been previously pursued by both industry and academia for indications other than AD.
One such target is the calcium-activated potassium channel KCa3.1 (KCNN4), which in the brain is primarily expressed in microglia and is significantly upregulated when microglia are activated.
We here review the existing evidence supporting that KCa3.1 inhibition could block microglial neurotoxicity without affecting their neuroprotective phagocytosis activity and without being broadly immunosuppressive.
The anti-inflammatory and neuroprotective effects of KCa3.1 blockade would be suitable for treating AD as well as cerebrovascular and traumatic brain injuries, two well-known risk factors contributing to the dementia in AD patients presenting with mixed pathologies.
Importantly, the pharmacokinetics and pharmacodynamics of several KCa3.1 blockers are well known, and a KCa3.1 blocker has been proven safe in clinical trials.
It is therefore promising to reposition old or new KCa3.1 blockers for AD preclinical and clinical trials.
American Psychological Association (APA)
Maezawa, Izumi& Jenkins, David Paul& Jin, Benjamin E.& Wulff, Heike. 2012. Microglial KCa3.1 Channels as a Potential Therapeutic Target for Alzheimer’s Disease. International Journal of Alzheimer's Disease،Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-504787
Modern Language Association (MLA)
Maezawa, Izumi…[et al.]. Microglial KCa3.1 Channels as a Potential Therapeutic Target for Alzheimer’s Disease. International Journal of Alzheimer's Disease No. 2012 (2012), pp.1-8.
https://search.emarefa.net/detail/BIM-504787
American Medical Association (AMA)
Maezawa, Izumi& Jenkins, David Paul& Jin, Benjamin E.& Wulff, Heike. Microglial KCa3.1 Channels as a Potential Therapeutic Target for Alzheimer’s Disease. International Journal of Alzheimer's Disease. 2012. Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-504787
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-504787