Decreased alpha-endosulfine, an endogenous regulator of ATP-sensitive potassium channels, in brains from adult Down syndrome patients
Alpha-endosulfine has the ability to block ATP-sensitive potassium (KATP) channels and stimulate insulin release in ß cells like sulfonylurea. Alpha-endosulfine is expressed in a wide range of tissue, including brain and endocrine tissues. Although KATP channels are also present in brain and its regulators have been reported to be involved in the release of neurotransmitters such as acetylcholine that plays an important role in cognitive function, the neurobiological role of α-endosulfine has not been studied yet. We examined the expression levels of α-endosulfine protein in frontal cortex and cerebellum from patients with Down syndrome (DS) showing Alzheimer’s disease (AD) pathology using Western blotting. In frontal cortex, α-endosulfine was detected in all of 10 controls, but only 1 (from female) out of 8 DS with weak density. In cerebellum, α-endosulfine was also detected in all of 9 controls, but only 1 (from male) out of 6 DS with weak density. The considerably decreased α-endosulfine could result in the continuous opening of KATP channels and the subsequent decrease of neurotransmitters release associated with cognition. This study is of significance providing evidence for a biological role of α-endosulfine in brain and α-endosulfine protein could be a pharmacological target for therapeutic intervention.
KeywordsFrontal Cortex Down Syndrome KATP Channel Impaired Glucose Metabolism Weak Density
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