Send to:

Choose Destination
See comment in PubMed Commons below
Int J Alzheimers Dis. 2012;2012:868972. doi: 10.1155/2012/868972. Epub 2012 May 22.

Microglial KCa3.1 Channels as a Potential Therapeutic Target for Alzheimer's Disease.

Author information

  • 1Department of Pathology and Laboratory Medicine, University of California Davis, Davis, CA 95616, USA.


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.

Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Hindawi Publishing Corporation Icon for PubMed Central
    Loading ...
    Write to the Help Desk