Research press release


Nature Medicine

Targeting chloride for neurological disease


KCC2は膜貫通型のポンプで、ニューロン内部の塩素イオン濃度を低く保つ働きをし、その働きで神経インパルスを阻害できる。そこでYves De Koninckたちは、KCC2を活性化できる薬があれば、阻害性シグナルを回復でき、神経疾患の治療に役立って、臨床的に期待できるかもしれないと考えた。Koninckたちは、低分子化合物ライブラリーをスクリーニングして、CLP257と呼ぶ化合物を見つけだした。さらに研究を進め、この化合物がKCC2の発現と活性を促進し、神経を損傷したラットの痛みを軽減させることを明らかにした。


The activity of the potassium-chloride membrane protein, KCC2, is reduced in many neurological and psychiatric disorders in humans, such as chronic pain, anxiety, and epilepsy. A study published online this week in Nature Medicine reports a newly-developed small molecule that can activate KCC2 and reduce chronic pain in rats. The findings suggest a promising therapeutic approach to treat pain and other conditions in which the KCC2 activity is impaired.

KCC2 is a transmembrane pump that keeps chloride ion concentrations low within neurons, which enables inhibition of nerve impulses. Therefore, Yves De Koninck and colleagues reason that a drug that could activate KCC2 may prove promising in the clinic to restore inhibitory signals and treat neurological diseases. The team screened a small molecule compound library and identify a drug, which they call CLP257. They go on to show that this drug can enhance KCC2 expression and its activity and reduce pain in rats with nerve injury.

They note that a related compound with better pharmacological profiles than CLP257 was as effective in reducing pain in rats as an existing pain treatment called pregabalin, but it lacked the undesirable motor side effects that are often seen with that drug.

doi: 10.1038/nm.3356


メールマガジンリストの「Nature 関連誌今週のハイライト」にチェックをいれていただきますと、毎週各ジャーナルからの最新の「注目のハイライト」をまとめて皆様にお届けいたします。