Alzheimer's disease (AD) is characterised by extracellular deposition of amyloid-β (Aβ) in amyloid plaques and intracellular aggregation and accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFTs). Although several kinases have been identified to contribute to the pathological phosphorylation of tau, kinase-targeted therapies for AD have not been successful in clinical trials. Critically, the kinases responsible for numerous identified tau phosphorylation sites remain unknown. G protein-coupled receptor (GPCR) kinases (GRKs) have recently been implicated in phosphorylation of non-GPCR substrates, for example, tubulin and α-synuclein, and in neurological disorders, including schizophrenia and Parkinson's disease. Accordingly, we investigated the involvement of GRKs in the pathophysiology of AD.

中文翻译：

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G蛋白偶联受体激酶与阿尔茨海默病病理学有关

阿尔茨海默病 (AD) 的特征在于淀粉样蛋白斑块中淀粉样蛋白-β (Aβ) 的细胞外沉积以及神经原纤维缠结 (NFT) 中过度磷酸化 tau 的细胞内聚集和积累。尽管已经鉴定出几种激酶有助于 tau 的病理磷酸化，但针对 AD 的激酶靶向疗法在临床试验中尚未成功。至关重要的是，负责许多已确定的 tau 磷酸化位点的激酶仍然未知。G 蛋白偶联受体 (GPCR) 激酶 (GRK) 最近与非 GPCR 底物的磷酸化有关，例如微管蛋白和 α-突触核蛋白，以及神经系统疾病，包括精神分裂症和帕金森病。因此，我们研究了 GRK 在 AD 病理生理学中的作用。