Genetic Variants of Lipoprotein Lipase and Regulatory Factors Associated with Alzheimer's Disease Risk.
Genetic Variants of Lipoprotein Lipase and Regulatory Factors Associated with Alzheimer's Disease Risk.
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DOI：
10.3390/ijms21218338
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发表时间：
2020-11-06
影响因子：
5.6
通讯作者：
H Eckel R
中科院分区：
文献类型：
--
作者：
D Bruce K;Tang M;Reigan P;H Eckel R
脂蛋白脂酶（LPL）是脂质和脂蛋白代谢的关键酶。LPL的典型作用包括水解富含磷脂酰肌醇的脂蛋白，为代谢组织提供FFA。然而，LPL也可能通过充当脂蛋白和细胞表面受体之间的分子桥梁而有助于脂蛋白摄取。最近的研究表明，LPL在脑中大量表达，并且主要在人和小鼠脑的巨噬细胞和小胶质细胞中表达。此外，最近的研究结果表明，LPL在小胶质细胞功能、代谢和细胞外因子如淀粉样蛋白-β（Aβ）的吞噬中起直接作用。虽然LPL在大脑中的确切功能仍有待确定，但一些研究表明LPL变体与阿尔茨海默病（AD）风险有关。例如，虽然突变显示对LPL功能和表达具有有害影响（例如，N291 S、HindIII和PvuII）与AD风险增加相关，与桥接功能增加相关的突变（S447 X）可能对AD具有保护作用。最近的研究还表明，内源性LPL激活剂（ApoC-II）和抑制剂（ApoC-III）的遗传变异可以分别增加和降低AD风险，这与LPL可能在AD发病机制中起保护作用的观点一致。在这里，我们回顾了最近的进展，我们了解LPL的结构和功能，这在很大程度上指出了功能性LPL在AD神经发病机制中的保护作用。
Lipoprotein lipase (LPL) is a key enzyme in lipid and lipoprotein metabolism. The canonical role of LPL involves the hydrolysis of triglyceride-rich lipoproteins for the provision of FFAs to metabolic tissues. However, LPL may also contribute to lipoprotein uptake by acting as a molecular bridge between lipoproteins and cell surface receptors. Recent studies have shown that LPL is abundantly expressed in the brain and predominantly expressed in the macrophages and microglia of the human and murine brain. Moreover, recent findings suggest that LPL plays a direct role in microglial function, metabolism, and phagocytosis of extracellular factors such as amyloid- beta (Aβ). Although the precise function of LPL in the brain remains to be determined, several studies have implicated LPL variants in Alzheimer’s disease (AD) risk. For example, while mutations shown to have a deleterious effect on LPL function and expression (e.g., N291S, HindIII, and PvuII) have been associated with increased AD risk, a mutation associated with increased bridging function (S447X) may be protective against AD. Recent studies have also shown that genetic variants in endogenous LPL activators (ApoC-II) and inhibitors (ApoC-III) can increase and decrease AD risk, respectively, consistent with the notion that LPL may play a protective role in AD pathogenesis. Here, we review recent advances in our understanding of LPL structure and function, which largely point to a protective role of functional LPL in AD neuropathogenesis.
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影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
影响因子：
32.4
作者：
Hammond, Timothy R.;Dufort, Connor;Stevens, Beth
通讯作者：
Stevens, Beth
影响因子：
3.4
作者：
Blain, Jean-Francois;Aumont, Nicole;Poirier, Judes
通讯作者：
Poirier, Judes
DOI：
10.1073/pnas.1820171116
发表时间：
2019-05-21
影响因子：
11.1
作者：
Arora, Rishi;Nimonkar, Amitabh V.;Trauger, John W.
通讯作者：
Trauger, John W.
脂蛋白脂肪酶（LPL）基因的印度和PVUII多态性降低了缺血性中风的风险（IS）：一项荟萃分析。
影响因子：
1.6
作者：
Cao L;Li Q;Chen X
通讯作者：
Chen X