Research press release


Nature Communications

Health: Newly-identified peptide targets traumatic brain injury



今回、Erkki Ruoslahtiたちは、2匹のTBIマウスモデル(穿通性脳損傷と非穿通性脳損傷のマウスモデル)を使って研究を行い、穿通性脳損傷マウスモデルにさまざまなペプチドを静注してから、脳内の損傷部位に滞留するペプチドを単離し、それがCAQKであることを明らかにした。次いでRuoslahtiたちは、CAQKが非穿通性脳損傷マウスモデルの損傷部位にも蓄積するが、他の損傷臓器(例えば、皮膚、肝臓)には蓄積しないことも明らかにした。CAQKは、少なくとも5日間にわたって損傷部位に到達していた。さらにRuoslahtiたちは、TBIマウスモデルの脳内で大量に産生される特定のタンパク質複合体にCAQKが結合することによってCAQKの滞留が起こるという考えを示している。


A specific peptide (CAQK) which targets traumatic brain injury (TBI) and may be used to deliver therapeutics to the brain, is identified in a study in mice published in Nature Communications this week. The peptide, which accumulates at the site of injury, could represent an important tool for TBI diagnosis and targeted therapy.

TBI is a type of acute brain injury comprising so-called ‘non-penetrating’ brain injuries (such as those caused by car accidents and some sport accidents) and so-called ‘penetrating’ brain injuries (such as those caused by gun shots or shrapnel during wars). With an annual incidence of 2.5 million people in the USA, TBI can lead to long-lasting disabilities and, at worst, death. Despite its socio-economic burden, diagnosis and treatment for TBI are still challenging, mainly due to low retention time of injected drugs and imaging probes, which are washed out quickly from the injury site by the blood flow.

Erkki Ruoslahti and colleagues study two TBI mouse models, one representing penetrating and the other non-penetrating brain injury. They intravenously inject various peptides into the mouse models for penetrating brain injury, and isolate and identify CAQK, which is retained in the brain at the site of injury. They then show that CAQK also accumulates at the site of injury in mouse models for non-penetrating brain injury but does not accumulate in other injured organs (such as skin and liver). The injury remains accessible to the peptide for at least up to five days. The authors further find that the peptide is retained through binding to a specific protein complex abundantly produced in TBI in the brains of the mice.

The authors note that the peptide binds to the same protein complex in cultured human cells and in sections of injured human brain tissue derived from patients. This work, although still preliminary, opens up the possibility of nanomedicine-based therapeutic approaches for human patients affected by TBI.

doi: 10.1038/ncomms11980

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