Poly (ADP-ribose) polymerases as PET imaging targets for central nervous system diseases.
Poly (ADP-ribose) polymerases as PET imaging targets for central nervous system diseases.
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DOI：
10.3389/fmed.2022.1062432
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发表时间：
2022
影响因子：
3.9
通讯作者：
中科院分区：
文献类型：
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作者：
聚（ADP-核糖）聚合酶 (PARP) 由 17 个成员组成，与不同的细胞过程相关，在 DNA 修复、染色质组织、基因组完整性、细胞凋亡和炎症中发挥着至关重要的作用。多种证据表明，激活的 PARP1 与强烈的 DNA 损伤和刺激性炎症反应有关，而这些反应又与各种神经系统疾病的病因有关。 PARP1/2 作为合理的治疗靶点引起了人们极大的兴趣，并且已经出现了多种 PARP1/2 抑制剂用于治疗癌症、代谢、炎症和神经系统疾病。此外，PARP1/2 作为成像靶标已被证明可以通过定位和量化 PARP1/2 的表达水平来检测、描述和预测许多疾病的治疗反应。 PARP1/2 导向的无创正电子发射断层扫描 (PET) 在诊断和预测神经系统疾病方面具有潜力。然而，由于开发血脑屏障（BBB）可穿透的 PARP 放射性配体的挑战，中枢神经系统（CNS）的定量 PARP PET 成像一直困扰着我们。在此，我们回顾了PARP1/2在中枢神经系统疾病中的相关性，总结了PARP PET的最新进展，并讨论了开发用于中枢神经系统疾病的新型PARP放射性示踪剂的可能性。
Poly (ADP-ribose) polymerases (PARPs) constitute of 17 members that are associated with divergent cellular processes and play a crucial role in DNA repair, chromatin organization, genome integrity, apoptosis, and inflammation. Multiple lines of evidence have shown that activated PARP1 is associated with intense DNA damage and irritating inflammatory responses, which are in turn related to etiologies of various neurological disorders. PARP1/2 as plausible therapeutic targets have attracted considerable interests, and multitudes of PARP1/2 inhibitors have emerged for treating cancer, metabolic, inflammatory, and neurological disorders. Furthermore, PARP1/2 as imaging targets have been shown to detect, delineate, and predict therapeutic responses in many diseases by locating and quantifying the expression levels of PARP1/2. PARP1/2-directed noninvasive positron emission tomography (PET) has potential in diagnosing and prognosing neurological diseases. However, quantitative PARP PET imaging in the central nervous system (CNS) has evaded us due to the challenges of developing blood-brain barrier (BBB) penetrable PARP radioligands. Here, we review PARP1/2's relevance in CNS diseases, summarize the recent progress on PARP PET and discuss the possibilities of developing novel PARP radiotracers for CNS diseases.
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DOI：
10.1126/science.aat8407
发表时间：
2018-11-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kam TI;Mao X;Park H;Chou SC;Karuppagounder SS;Umanah GE;Yun SP;Brahmachari S;Panicker N;Chen R;Andrabi SA;Qi C;Poirier GG;Pletnikova O;Troncoso JC;Bekris LM;Leverenz JB;Pantelyat A;Ko HS;Rosenthal LS;Dawson TM;Dawson VL
通讯作者：
Dawson VL
影响因子：
9.3
作者：
Carney, Brandon;Kossatz, Susanne;Reiner, Thomas
通讯作者：
Reiner, Thomas
影响因子：
4.8
作者：
Ge, WW;Wen, WY;Strong, MJ
通讯作者：
Strong, MJ
影响因子：
3.1
作者：
Guibbal, Florian;Hopkins, Samantha L.;Cornelissen, Bart
通讯作者：
Cornelissen, Bart
影响因子：
4.2
作者：
Kauppinen, TM;Suh, SW;Swanson, RA
通讯作者：
Swanson, RA