Controlling Calcium-- Ion Channels and Familial Alzheimer's

Having the chance to hear Erika Piedras speak of her research on neuronal calcium channels and their relation to leptin resistance and homeostatic mechanisms in mice back in September, I began getting curious about what kind of common ailments and illnesses occur with relation to this type of neuronal system.  Her 2007 paper Voltage-gated calcium channels, calcium signaling, and channelopathies offers insight to the mechanisms of voltage-gated calcium channels (VGCCs), and states some linkages discovered between VGCCs and genetic diseases. Looking further into this topic on the (e) Science News website, I stumbled upon an interesting article about the role of calcium ion channeling and its relationship to familial Alzheimer's disease (FAD).

Research conducted by Kevin Foskett and other researchers at the University of Pennsylvania Perelman School of Medicine has linked genetic mutations in neural presenilin proteins to FAD. This research began when Foskett and colleagues found linkages between presenilin mutations (primarily, those in the PS1 and PS2 proteins) and their interactions with IP3R (the Ca²⁺ ion release channel) in mice: most importantly, that mutated PS1 and PS2 proteins interacted with IP3R receptors in such a way that neural Ca²⁺ ion flow was increased. They began to hypothesize about possible consequences between genetically altered PS proteins with IP3R receptors, and how these mutations could be related to the development of symptoms related to FAD.

By experimenting on mice modeled with FAD and then performing behavioral tests, the team showed that reducing an IP3R receptor (called IP3R₁) by 50% normalized the overexcited Ca²⁺ flow in the hippocampus which, in turn, reduced memory deficits and defective electrical signaling—both of which are common symptoms of FAD and other dementia-related illnesses. This project has shed new light on this genetic condition that affects close to a quarter million Americans, and could offer further connections to the non-genetic Alzheimer’s spectrum that affects another 4.5 million.

Sources:

Piedras, E. (2007, July 27). Voltage-gated calcium channels, calcium signaling, and channelopathies. Retrieved October 10, 2015.

Role of calcium in familial Alzheimer's disease clarified, pointing to new therapeutics. (2014, May 14). Retrieved October 10, 2015, from http://esciencenews.com/articles/2014/05/14/role.calcium.familial.alzheimers.disease.clarified.pointing.new.therapeutics

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