Genetic knockdown of Klk8 has sex-specific multi-targeted therapeutic effects on Alzheimer’s pathology in mice,Neuropathology and Applied Neurobiology

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Genetic knockdown of Klk8 has sex-specific multi-targeted therapeutic effects on Alzheimer’s pathology in mice
Neuropathology and Applied Neurobiology ( IF 4.0 ) Pub Date : 2020-12-20 , DOI: 10.1111/nan.12687
Arne Herring ₁ , Nirup K Kurapati ₁ , Sofia Krebs ₁ , Nils Grammon ₁ , Luisa M Scholz ₁ , Gerrit Voss ₁ , Muhammad R Miah ₁ , Vanessa Budny ₁ , Fabian Mairinger ₂ , Katharina Haase ₁ , Sarah Teuber-Hanselmann ₁ , Celia Dobersalske ₃ , Sara Schramm ₄ , Karl-Heinz Jöckel ₄ , Yvonne Münster ₁ , Kathy Keyvani ₁

Affiliation

Previous work in our lab has identified the protease kallikrein-8 (KLK8) as a potential upstream mover in the pathogenesis of Alzheimer’s disease (AD). We showed pathologically elevated levels of KLK8 in the cerebrospinal fluid and blood of patients with mild cognitive impairment or dementia due to AD, and in brains of patients and transgenic CRND8 (TgCRND8) mice in incipient stages of the disease. Furthermore, short-term antibody-mediated KLK8 inhibition in moderate stage disease alleviated AD pathology in female mice. However, it remains to be shown whether long-term reversal of KLK8 overexpression can also counteract AD. Therefore, the effects of genetic Klk8-knockdown were determined in TgCRND8 mice.

中文翻译：

Klk8基因敲除对小鼠阿尔茨海默病病理具有性别特异性多靶向治疗作用

我们实验室以前的工作已将蛋白酶激肽释放酶 8 (KLK8) 确定为阿尔茨海默病 (AD) 发病机制中的潜在上游推动者。我们发现，由于 AD 导致的轻度认知障碍或痴呆患者的脑脊液和血液中，以及处于疾病初期的患者和转基因 CRND8 (TgCRND8) 小鼠的大脑中，KLK8 的水平出现病理性升高。此外，在中度疾病中短期抗体介导的 KLK8 抑制减轻了雌性小鼠的 AD 病理学。然而，KLK8 过度表达的长期逆转是否也可以抵消 AD 仍有待证明。因此，在 TgCRND8 小鼠中确定了基因Klk 8 敲低的影响。

更新日期：2020-12-20

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