RIG-1 receptor expression in the pathology of Alzheimer's disease

被引:27
作者
Vaccari, Juan Pablo de Rivero [1 ,5 ]
Brand, Frank J., III [2 ]
Sedaghat, Christina [5 ]
Mash, Deborah C. [3 ,4 ]
Dietrich, W. Dalton [1 ,5 ]
Keane, Robert W. [2 ,5 ]
机构
[1] Univ Miami, Miller Sch Med, Dept Neurol Surg, Miami, FL 33136 USA
[2] Univ Miami, Miller Sch Med, Dept Physiol & Biophys, Miami, FL 33136 USA
[3] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA
[4] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA
[5] Univ Miami, Miller Sch Med, Miami Project Cure Paralysis, Miami, FL 33136 USA
关键词
Innate immunity; Rig signaling; RLR; Inflammation; Alzheimer's disease; Mild cognitive impairment; MILD COGNITIVE IMPAIRMENT; AMYLOID PRECURSOR PROTEIN; INNATE IMMUNE-SYSTEM; BETA-PEPTIDE; INFLAMMATION; ACTIVATION; POPULATION; ASTROCYTES; MECHANISM; CYTOKINES;
D O I
10.1186/1742-2094-11-67
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease (AD) and involves activation of the innate immune response via recognition of diverse stimuli by pattern recognition receptors (PRRs). The inflammatory inducers and precise innate signaling pathway contributing to AD pathology remain largely undefined. Results: In the present study we analyzed expression levels of innate immune proteins in temporal and occipital cortices from preclinical (no cognitive impairment, NCI, N = 22) to mild cognitive impairment (MCI, N = 20) associated with AD pathology (N = 20) and AD patients (N = 23). We found that retinoic acid-inducible gene-I (RIG-1) is significantly elevated in the temporal cortex and plasma in patients with MCI. In addition, primary human astrocytes stimulated with the RIG-1 ligand 5'ppp RNA showed increased expression of amyloid precursor protein (APP) and amyloid-beta (A beta), supporting the idea that RIG-1 is involved in the pathology of MCI associated with early progression to AD. Conclusion: These findings suggest that RIG-1 may play a critical role in incipient AD.
引用
收藏
页数:9
相关论文
共 44 条
[1]   Amyloid-β Aggregates Cause Alterations of Astrocytic Metabolic Phenotype: Impact on Neuronal Viability [J].
Allaman, Igor ;
Gavillet, Mathilde ;
Belanger, Mireille ;
Laroche, Thierry ;
Viertl, David ;
Lashuel, Hilal A. ;
Magistretti, Pierre J. .
JOURNAL OF NEUROSCIENCE, 2010, 30 (09) :3326-3338
[2]   Alzheimer's Association Report 2011 Alzheimer's disease facts and figures [J].
Thies W. ;
Bleiler L. .
ALZHEIMERS & DEMENTIA, 2011, 7 (02) :208-244
[3]   NEUROPATHOLOGICAL STAGING OF ALZHEIMER-RELATED CHANGES [J].
BRAAK, H ;
BRAAK, E .
ACTA NEUROPATHOLOGICA, 1991, 82 (04) :239-259
[4]   Amyloid-β25-35 induces a permanent phosphorylation of HSF-1, but a transitory and inflammation-independent overexpression of Hsp-70 in C6 astrocytoma cells [J].
Calvillo, Minerva ;
Diaz, Alfonso ;
Limon, Daniel I. ;
Angel Mayoral, Miguel ;
Elena Chanez-Cardenas, Maria ;
Zenteno, Edgar ;
Montano, Luis F. ;
Guevara, Jorge ;
Espinosa, Blanca .
NEUROPEPTIDES, 2013, 47 (05) :339-346
[5]   Astrogliosis involves activation of retinoic acid-inducible gene-like signaling in the innate immune response after spinal cord injury [J].
de Rivero Vaccari, Juan Pablo ;
Minkiewicz, Julia ;
Wang, Xiaoliang ;
De Rivero Vaccari, Juan Carlos ;
German, Ramon ;
Marcillo, Alex E. ;
Dietrich, W. Dalton ;
Keane, Robert W. .
GLIA, 2012, 60 (03) :414-421
[6]   DEMENTIA - DIAGNOSIS AND EVALUATION [J].
FLEMING, KC ;
ADAMS, AC ;
PETERSEN, RC .
MAYO CLINIC PROCEEDINGS, 1995, 70 (11) :1093-1107
[7]   Amyloid-β and Alzheimer's disease type pathology differentially affects the calcium signalling toolkit in astrocytes from different brain regions [J].
Grolla, A. A. ;
Sim, J. A. ;
Lim, D. ;
Rodriguez, J. J. ;
Genazzani, A. A. ;
Verkhratsky, A. .
CELL DEATH & DISEASE, 2013, 4 :e623-e623
[8]   Alzheimer disease in the US population - Prevalence estimates using the 2000 census [J].
Hebert, LE ;
Scherr, PA ;
Bienias, JL ;
Bennett, DA ;
Evans, DA .
ARCHIVES OF NEUROLOGY, 2003, 60 (08) :1119-1122
[9]   5′-triphosphate RNA is the ligand for RIG-I [J].
Hornung, Veit ;
Ellegast, Jana ;
Kim, Sarah ;
Brzozka, Krzysztof ;
Jung, Andreas ;
Kato, Hiroki ;
Poeck, Hendrik ;
Akira, Shizuo ;
Conzelmann, Karl-Klaus ;
Schlee, Martin ;
Endres, Stefan ;
Hartmann, Gunther .
SCIENCE, 2006, 314 (5801) :994-997
[10]   Toll-like receptor 4-dependent upregulation of cytokines in a transgenic mouse model of Alzheimer's disease [J].
Jin, Jing-Ji ;
Kim, Hong-Duck ;
Maxwell, J. Adam ;
Li, Ling ;
Fukuchi, Ken-ichiro .
JOURNAL OF NEUROINFLAMMATION, 2008, 5 (1)