Alzheimer's genes in microglia: a risk worth investigating.

Alzheimer's genes in microglia: a risk worth investigating.
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小胶质细胞中的阿尔茨海默病基因:一个值得研究的风险。

DOI:
10.1186/s13024-023-00679-4
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发表时间:
2023-11-20
影响因子:
15.1
通讯作者:
Thinakaran, Gopal
Thinakaran, Gopal
中科院分区:
医学1区
文献类型:
--
作者:
Sudwarts, Ari;Thinakaran, Gopal

文献摘要

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相似文献

尽管表达了许多关键的风险基因,但小胶质细胞在迟发性阿尔茨海默病病理生理学中的作用有些模糊,据报道,各种表型是有害的或保护性的。在此,我们回顾了临床和动物模型研究的一些关键发现,讨论了小胶质细胞遗传学在介导稳态扰动中的作用。我们注意到,对保护性表型的损害可能包括小胶质细胞活化延长或不足,导致代谢组学(特别是脂质相关)过程失调,并伴有动态反应中与年龄相关的可耐受性。小鼠遗传学和侵略性的转基因建模的不确定性意味着严重的局限性,在应用目前的方法进行病因学调查。尽管存在这些缺点,但广泛使用的淀粉样变性和tau蛋白病模型已被证明在解剖小胶质细胞对AD病理生理学的功能反应方面是非常宝贵的。最近的一些进展使建模工具更接近人类遗传学,增加了病因学和翻译努力的有效性。
Despite expressing many key risk genes, the role of microglia in late-onset Alzheimer’s disease pathophysiology is somewhat ambiguous, with various phenotypes reported to be either harmful or protective. Herein, we review some key findings from clinical and animal model investigations, discussing the role of microglial genetics in mediating perturbations from homeostasis. We note that impairment to protective phenotypes may include prolonged or insufficient microglial activation, resulting in dysregulated metabolomic (notably lipid-related) processes, compounded by age-related inflexibility in dynamic responses. Insufficiencies of mouse genetics and aggressive transgenic modelling imply severe limitations in applying current methodologies for aetiological investigations. Despite the shortcomings, widely used amyloidosis and tauopathy models of the disease have proven invaluable in dissecting microglial functional responses to AD pathophysiology. Some recent advances have brought modelling tools closer to human genetics, increasing the validity of both aetiological and translational endeavours.
DOI: 10.1038/s41588-022-01024-z
发表时间: 2022-04
期刊: NATURE GENETICS
影响因子: 30.8
作者:
Bellenguez, Celine;Kucukali, Fahri;Jansen, Iris E.;Kleineidam, Luca;Moreno-Grau, Sonia;Amin, Najaf;Naj, Adam C.;Campos-Martin, Rafael;Grenier-Boley, Benjamin;Andrade, Victor;Holmans, Peter A.;Boland, Anne;Damotte, Vincent;van der Lee, Sven J.;Costa, Marcos R.;Kuulasmaa, Teemu;Yang, Qiong;De Rojas, Itziar;Bis, Joshua C.;Yaqub, Amber;Prokic, Ivana;Chapuis, Julien;Ahmad, Shahzad;Giedraitis, Vilmantas;Aarsland, Dag;Garcia-Gonzalez, Pablo;Abdelnour, Carla;Alarcon-Martin, Emilio;Alcolea, Daniel;Alegret, Montserrat;Alvarez, Ignacio;Alvarez, Victoria;Armstrong, Nicola J.;Tsolaki, Anthoula;Antunez, Carmen;Appollonio, Ildebrando;Arcaro, Marina;Archetti, Silvana;Arias Pastor, Alfonso;Arosio, Beatrice;Athanasiu, Lavinia;Bailly, Henri;Banaj, Nerisa;Baquero, Miquel;Barral, Sandra;Beiser, Alexa;Pastor, Ana Belen;Below, Jennifer E.;Benchek, Penelope;Benussi, Luisa;Berr, Claudine;Besse, Celine;Bessi, Valentina;Binetti, Giuliano;Bizarro, Alessandra;Blesa, Rafael;Boada, Merce;Boerwinkle, Eric;Borroni, Barbara;Boschi, Silvia;Bossu, Paola;Brathen, Geir;Bressler, Jan;Bresner, Catherine;Brodaty, Henry;Brookes, Keeley J.;Ignacio Brusco, Luis;Buiza-Rueda, Dolores;Burger, Katharina;Burholt, Vanessa;Bush, William S.;Calero, Miguel;Cantwell, Laura B.;Chene, Genevieve;Chung, Jaeyoon;Cuccaro, Michael L.;Cecchetti, Roberta;Cervera-Carles, Laura;Charbonnier, Camille;Chen, Hung-Hsin;Chillotti, Caterina;Ciccone, Simona;Claassen, Jurgen A. 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通讯作者: Lambert, Jean-Charles
DOI: 10.1111/j.1471-4159.2010.06595.x
发表时间: 2010-04
影响因子: 4.7
作者:
Ager RR;Fonseca MI;Chu SH;Sanderson SD;Taylor SM;Woodruff TM;Tenner AJ
通讯作者: Tenner AJ
DOI: 10.1016/j.neuron.2010.08.023
发表时间: 2010-10-06
期刊: NEURON
影响因子: 16.2
作者:
Bhaskar, Kiran;Konerth, Megan;Kokiko-Cochran, Olga N.;Cardona, Astrid;Ransohoff, Richard M.;Lamb, Bruce T.
通讯作者: Lamb, Bruce T.
DOI: 10.1042/0264-6021:3440375
发表时间: 1999-12-01
影响因子: 4.1
作者:
Calero, M;Tokuda, T;Ghiso, J
通讯作者: Ghiso, J
DOI: 10.1186/s13024-017-0216-6
发表时间: 2017-10-16
影响因子: 15.1
作者:
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通讯作者: Lamb BT