GPCR, a rider of Alzheimer’s disease

Xiaosong LIU, Jian ZHAO

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Front. Biol. ›› 2011, Vol. 6 ›› Issue (4) : 282-288. DOI: 10.1007/s11515-011-1129-3
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GPCR, a rider of Alzheimer’s disease

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Abstract

Alzheimer’s disease (AD) is the most common type of dementia that affects thinking, learning, memory and behavior of older people. Based on the previous studies, three pathogenic pathways are now commonly accepted as the culprits of this disease namely, amyloid-β pathway, tauopathology and cholinergic dysfunction. This review focuses on the current findings on the regulatory roles of G protein-coupled receptors (GPCRs) in the pathological progression of AD and discusses the potential of the GPCRs as novel therapeutic targets for AD.

Keywords

Alzheimer’s disease (AD) / G protein-coupled receptors (GPCRs) / secretase / amyloid-β / tau

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Xiaosong LIU, Jian ZHAO. GPCR, a rider of Alzheimer’s disease. Front Biol, 2011, 6(4): 282‒288 https://doi.org/10.1007/s11515-011-1129-3

References

[1]
AbdAlla S, Lother H, el Missiry A, Langer A, Sergeev P, el Faramawy Y, Quitterer U (2009).Angiotensin II AT2 receptor oligomers mediate G-protein dysfunction in an animal model of Alzheimer disease. J Biol Chem, 284: 6554–6565
CrossRef Pubmed Google scholar
[2]
Alonso A C, Grundke-Iqbal I, Iqbal K (1996). Alzheimer’s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat Med, 2(7): 783–787
CrossRef Pubmed Google scholar
[3]
Alonso A C, Zaidi T, Grundke-Iqbal I, Iqbal K (1994). Role of abnormally phosphorylated tau in the breakdown of microtubules in Alzheimer disease. Proc Natl Acad Sci USA, 91(12): 5562–5566
CrossRef Pubmed Google scholar
[4]
Arjona A A, Pooler A M, Lee R K, Wurtman R J (2002). Effect of a 5-HT(2C) serotonin agonist, dexnorfenfluramine, on amyloid precursor protein metabolism in guinea pigs. Brain Res, 951(1): 135–140
CrossRef Pubmed Google scholar
[5]
Arriagada P V, Growdon J H, Hedley-Whyte E T, Hyman B T (1992). Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology, 42(3 Pt 1): 631–639
Pubmed
[6]
Asai M, Hattori C, Szabó B, Sasagawa N, Maruyama K, Tanuma S, Ishiura S (2003). Putative function of ADAM9, ADAM10, and ADAM17 as APP alpha-secretase. Biochem Biophys Res Commun, 301(1): 231–235
CrossRef Pubmed Google scholar
[7]
Ashe K H (2007). A tale about tau. N Engl J Med, 357(9): 933–935
CrossRef Pubmed Google scholar
[8]
Ballatore C, Lee V M, Trojanowski J Q (2007). Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci, 8(9): 663–672
CrossRef Pubmed Google scholar
[9]
Baxter M G, Chiba A A (1999). Cognitive functions of the basal forebrain. Curr Opin Neurobiol, 9(2): 178–183
CrossRef Pubmed Google scholar
[10]
Blalock E M, Geddes J W, Chen K C, Porter N M, Markesbery W R, Landfield P W (2004). Incipient Alzheimer’s disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc Natl Acad Sci USA, 101(7): 2173–2178
CrossRef Pubmed Google scholar
[11]
Bramham C R, Milgram N W, Srebro B (1991). Delta opioid receptor activation is required to induce LTP of synaptic transmission in the lateral perforant path in vivo. Brain Res, 567(1): 42–50
CrossRef Pubmed Google scholar
[12]
Brunden K R, Trojanowski J Q, Lee V M (2009). Advances in tau-focused drug discovery for Alzheimer’s disease and related tauopathies. Nat Rev Drug Discov, 8(10): 783–793
CrossRef Pubmed Google scholar
[13]
Budde T (2006). AICD treatment in 2004—state of the art. Eur J Med Res, 11(10): 432–438
Pubmed
[14]
Caccamo A, Oddo S, Billings L M, Green K N, Martinez-Coria H, Fisher A, LaFerla F M (2006). M1 receptors play a central role in modulating AD-like pathology in transgenic mice. Neuron, 49(5): 671–682
CrossRef Pubmed Google scholar
[15]
Chartier-Harlin M C, Crawford F, Houlden H, Warren A, Hughes D, Fidani L, Goate A, Rossor M, Roques P, Hardy J, Mullan M (1991). Early-onset Alzheimer’s disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. Nature, 353(6347): 844–846
CrossRef Pubmed Google scholar
[16]
Citron M (2010). Alzheimer’s disease: strategies for disease modification. Nat Rev Drug Discov, 9(5): 387–398
CrossRef Pubmed Google scholar
[17]
Doraiswamy P M, Xiong G L (2006). Pharmacological strategies for the prevention of Alzheimer’s disease. Expert Opin Pharmacother, 7(1): 1–10
CrossRef Pubmed Google scholar
[18]
El Khoury J, Toft M, Hickman S E, Means T K, Terada K, Geula C, Luster A D (2007). Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med, 13(4): 432–438
CrossRef Pubmed Google scholar
[19]
Ferraguti F, Baldani-Guerra B, Corsi M, Nakanishi S, Corti C (1999). Activation of the extracellular signal-regulated kinase 2 by metabotropic glutamate receptors. Eur J Neurosci, 11(6): 2073–2082
CrossRef Pubmed Google scholar
[20]
Fisher A (2008). Cholinergic treatments with emphasis on m1 muscarinic agonists as potential disease-modifying agents for Alzheimer’s disease. Neurotherapeutics, 5(3): 433–442
CrossRef Pubmed Google scholar
[21]
Francis R, McGrath G, Zhang J, Ruddy D A, Sym M, Apfeld J, Nicoll M, Maxwell M, Hai B, Ellis M C, Parks A L, Xu W, Li J, Gurney M, Myers R L, Himes C S, Hiebsch R, Ruble C, Nye J S, Curtis D (2002). aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation. Dev Cell, 3(1): 85–97
CrossRef Pubmed Google scholar
[22]
Gallagher M, King R A, Young N B (1983). Opiate antagonists improve spatial memory. Science, 221(4614): 975–976
CrossRef Pubmed Google scholar
[23]
Gilman A G (1987). G proteins: transducers of receptor-generated signals. Annu Rev Biochem, 56(1): 615–649
CrossRef Pubmed Google scholar
[24]
Goate A, Chartier-Harlin M C, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, Mant R, Newton P, Rooke K, Roques P, Talbot C, Pericak-Vance M, Roses A, Williamson R, Rossor M, Owen M, Hardy J (1991). Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature, 349(6311): 704–706
CrossRef Pubmed Google scholar
[25]
Goedert M, Spillantini M G (2006). A century of Alzheimer’s disease. Science, 314(5800): 777–781
CrossRef Pubmed Google scholar
[26]
Gomez-Isla T, Hollister R, West H, Mui S, Growdon J H, Petersen R C, Parisi J E, Hyman B T (1997). Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer’s disease. Ann Neurol, 41(1): 17–24
CrossRef Pubmed Google scholar
[27]
Gong C X, Iqbal K (2008). Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Curr Med Chem, 15(23): 2321–2328
CrossRef Pubmed Google scholar
[28]
Hanger D P, Anderton B H, Noble W (2009). Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med, 15(3): 112–119
CrossRef Pubmed Google scholar
[29]
Hesselgesser J, Horuk R (1999). Chemokine and chemokine receptor expression in the central nervous system. J Neurovirol, 5(1): 13–26
CrossRef Pubmed Google scholar
[30]
Hu Y, Fortini M E (2003). Different cofactor activities in gamma-secretase assembly: evidence for a nicastrin-Aph-1 subcomplex. J Cell Biol, 161(4): 685–690
CrossRef Pubmed Google scholar
[31]
Iismaa T P, Kiefer J, Liu M L, Baker E, Sutherland G R, Shine J (1994). Isolation and chromosomal localization of a novel human G-protein-coupled receptor (GPR3) expressed predominantly in the central nervous system. Genomics, 24(2): 391–394
CrossRef Pubmed Google scholar
[32]
Ittner L M, Ke Y D, Delerue F, Bi M, Gladbach A, van Eersel J, Wölfing H, Chieng B C, Christie M J, Napier I A, Eckert A, Staufenbiel M, Hardeman E, Götz J (2010). Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models. Cell, 142(3): 387–397
CrossRef Pubmed Google scholar
[33]
Iwata N, Tsubuki S, Takaki Y, Shirotani K, Lu B, Gerard N P, Gerard C, Hama E, Lee H J, Saido T C (2001). Metabolic regulation of brain Abeta by neprilysin. Science, 292(5521): 1550–1552
CrossRef Pubmed Google scholar
[34]
Ladner C J, Lee J M (1998). Pharmacological drug treatment of Alzheimer disease: the cholinergic hypothesis revisited. J Neuropathol Exp Neurol, 57(8): 719–731
CrossRef Pubmed Google scholar
[35]
LaFerla F M, Green K N, Oddo S (2007). Intracellular amyloid-beta in Alzheimer’s disease. Nat Rev Neurosci, 8(7): 499–509
CrossRef Pubmed Google scholar
[36]
Lee H G, Ogawa O, Zhu X, O’Neill M J, Petersen R B, Castellani R J, Ghanbari H, Perry G, Smith M A (2004). Aberrant expression of metabotropic glutamate receptor 2 in the vulnerable neurons of Alzheimer’s disease. Acta Neuropathol, 107(4): 365–371
CrossRef Pubmed Google scholar
[37]
Lee V M, Goedert M, Trojanowski J Q (2001). Neurodegenerative tauopathies. Annu Rev Neurosci, 24(1): 1121–1159
CrossRef Pubmed Google scholar
[38]
Lefkowitz R J (2007). Seven transmembrane receptors: something old, something new. Acta Physiol (Oxf), 190(1): 9–19
CrossRef Pubmed Google scholar
[39]
Lefkowitz R J, Shenoy S K (2005). Transduction of receptor signals by beta-arrestins. Science, 308(5721): 512–517
CrossRef Pubmed Google scholar
[40]
Leissring M A, Farris W, Chang A Y, Walsh D M, Wu X, Sun X, Frosch M P, Selkoe D J (2003). Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron, 40(6): 1087–1093
CrossRef Pubmed Google scholar
[41]
Liu W H, Chang L S(2010). Suppression of ADAM17-mediated Lyn/Akt pathways induces apoptosis of human leukemia U937 cells BUNGARUS MULTICINCTUS PROTEASE INHIBITOR-LIKE PROTEIN-1 UNCOVERS THE CYTOTOXIC MECHANISM, J Biol Chem, 285(40): 30506–30515
[42]
Lleo A, Greenberg S M, Growdon J H (2006). Current pharmacotherapy for Alzheimer’s disease. Annu Rev Med, 57(1): 513–533
CrossRef Pubmed Google scholar
[43]
Martin Prince J J, Jackson J, eds (2010). Alzheimer’s Disease International, World Alzheimer Report 2009
[44]
Mathieu-Kia A M, Fan L Q, Kreek M J, Simon E J, Hiller J M (2001). Mu-, delta- and kappa-opioid receptor populations are differentially altered in distinct areas of postmortem brains of Alzheimer’s disease patients. Brain Res, 893(1-2): 121–134
CrossRef Pubmed Google scholar
[45]
Matsuo E S, Shin R W, Billingsley M L, Van deVoorde A, O’Connor M, Trojanowski J Q, Lee V M (1994). Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer’s disease paired helical filament tau. Neuron, 13(4): 989–1002
CrossRef Pubmed Google scholar
[46]
Mesulam M M, Mufson E J, Wainer B H, Levey A I (1983). Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1-Ch6). Neuroscience, 10(4): 1185–1201
CrossRef Pubmed Google scholar
[47]
Mills J, Laurent Charest D, Lam F, Beyreuther K, Ida N, Pelech S L, Reiner P B (1997). Regulation of amyloid precursor protein catabolism involves the mitogen-activated protein kinase signal transduction pathway. J Neurosci, 17(24): 9415–9422
Pubmed
[48]
Murrell J, Farlow M, Ghetti B, Benson M D (1991). A mutation in the amyloid precursor protein associated with hereditary Alzheimer’s disease. Science, 254(5028): 97–99
CrossRef Pubmed Google scholar
[49]
Necula M, Kuret J (2004). Pseudophosphorylation and glycation of tau protein enhance but do not trigger fibrillization in vitro. J Biol Chem, 279(48): 49694–49703
CrossRef Pubmed Google scholar
[50]
Ni Y, Zhao X, Bao G, Zou L, Teng L, Wang Z, Song M, Xiong J, Bai Y, Pei G (2006). Activation of beta2-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation. Nat Med, 12(12): 1390–1396
CrossRef Pubmed Google scholar
[51]
Nitsch R M, Deng M, Growdon J H, Wurtman R J (1996). Serotonin 5-HT2a and 5-HT2c receptors stimulate amyloid precursor protein ectodomain secretion. J Biol Chem, 271(8): 4188–4194
CrossRef Pubmed Google scholar
[52]
Phillips T, Barnes A, Scott S, Emson P, Rees S (1998). Human metabotropic glutamate receptor 2 couples to the MAP kinase cascade in chinese hamster ovary cells. Neuroreport, 9(10): 2335–2339
CrossRef Pubmed Google scholar
[53]
Pierce K L, Premont R T, Lefkowitz R J (2002). Seven-transmembrane receptors. Nat Rev Mol Cell Biol, 3(9): 639–650
CrossRef Pubmed Google scholar
[54]
Qiu W Q, Ye Z, Kholodenko D, Seubert P, Selkoe D J (1997). Degradation of amyloid beta-protein by a metalloprotease secreted by microglia and other neural and non-neural cells. J Biol Chem, 272(10): 6641–6646
CrossRef Pubmed Google scholar
[55]
Ray S, Britschgi M, Herbert C, Takeda-Uchimura Y, Boxer A, Blennow K, Friedman L F, Galasko D R, Jutel M, Karydas A, Kaye J A, Leszek J, Miller B L, Minthon L, Quinn J F, Rabinovici G D, Robinson W H, Sabbagh M N, So Y T, Sparks D L, Tabaton M, Tinklenberg J, Yesavage J A, Tibshirani R, Wyss-Coray T (2007). Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins. Nat Med, 13(11): 1359–1362
CrossRef Pubmed Google scholar
[56]
Roberson E D, Mucke L (2006). 100 years and counting: prospects for defeating Alzheimer’s disease. Science, 314(5800): 781–784
CrossRef Pubmed Google scholar
[57]
Rogaev E I, Sherrington R, Rogaeva E A, Levesque G, Ikeda M, Liang Y, Chi H, Lin C, Holman K, Tsuda T, Mar L, Sorbi S, Nacmias B, Piacentini S, Amaducci L, Chumakov I, Cohen D, Lannfelt L, Fraser P E, Rommens J M, George-Hyslop P H S (1995). Familial Alzheimer’s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type 3 gene. Nature, 376(6543): 775–778
CrossRef Pubmed Google scholar
[58]
Russo-Neustadt A, Cotman C W (1997). Adrenergic receptors in Alzheimer’s disease brain: selective increases in the cerebella of aggressive patients. J Neurosci, 17(14): 5573–5580
Pubmed
[59]
Saito T, Iwata N, Tsubuki S, Takaki Y, Takano J, Huang S M, Suemoto T, Higuchi M, Saido T C (2005). Somatostatin regulates brain amyloid beta peptide Aβ42 through modulation of proteolytic degradation. Nat Med, 11(4): 434–439
CrossRef Pubmed Google scholar
[60]
Selkoe D J (2001). Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev, 81(2): 741–766
Pubmed
[61]
Shahani N, Brandt R (2002). Functions and malfunctions of the tau proteins. Cell Mol Life Sci, 59(10): 1668–1680
CrossRef Pubmed Google scholar
[62]
Sherrington R, Rogaev E I, Liang Y, Rogaeva E A, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin J F, Bruni A C, Montesi M P, Sorbi S, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Brookes A, Sanseau P, Polinsky R J, Wasco W, Da Silva H A, Haines J L, Perkicak-Vance M A, Tanzi R E, Roses A D, Fraser P E, Rommens J M, St George-Hyslop P H (1995). Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature, 375(6534): 754–760
CrossRef Pubmed Google scholar
[63]
Sinha S, Anderson J P, Barbour R, Basi G S, Caccavello R, Davis D, Doan M, Dovey H F, Frigon N, Hong J, Jacobson-Croak K, Jewett N, Keim P, Knops J, Lieberburg I, Power M, Tan H, Tatsuno G, Tung J, Schenk D, Seubert P, Suomensaari S M, Wang S, Walker D, Zhao J, McConlogue L, John V (1999). Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature, 402(6761): 537–540
CrossRef Pubmed Google scholar
[64]
Sinha S, Lieberburg I (1999). Cellular mechanisms of beta-amyloid production and secretion. Proc Natl Acad Sci USA, 96(20): 11049–11053
CrossRef Pubmed Google scholar
[65]
Sisodia S S, St George-Hyslop P H (2002). gamma-Secretase, Notch, Abeta and Alzheimer’s disease: where do the presenilins fit in? Nat Rev Neurosci, 3(4): 281–290
CrossRef Pubmed Google scholar
[66]
Solano D C, Sironi M, Bonfini C, Solerte S B, Govoni S, Racchi M (2000). Insulin regulates soluble amyloid precursor protein release via phosphatidyl inositol 3 kinase-dependent pathway. FASEB J, 14(7): 1015–1022
Pubmed
[67]
Strittmatter W J, Saunders A M, Schmechel D, Pericak-Vance M, Enghild J, Salvesen G S, Roses A D (1993). Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA, 90(5): 1977–1981
CrossRef Pubmed Google scholar
[68]
Tabet N, Feldman H (2002). Indomethacin for the treatment of Alzheimer’s disease patients. Cochrane Database Syst Rev, (2): CD003673
Pubmed
[69]
Takasugi N, Tomita T, Hayashi I, Tsuruoka M, Niimura M, Takahashi Y, Thinakaran G, Iwatsubo T (2003). The role of presenilin cofactors in the gamma-secretase complex. Nature, 422(6930): 438–441
CrossRef Pubmed Google scholar
[70]
Teng L, Zhao J, Wang F, Ma L, Pei G (2010). A GPCR/secretase complex regulates beta- and gamma-secretase specificity for Abeta production and contributes to AD pathogenesis. Cell Res, 20(2): 138–153
CrossRef Pubmed Google scholar
[71]
Thathiah A, Spittaels K, Hoffmann M, Staes M, Cohen A, Horré K, Vanbrabant M, Coun F, Baekelandt V, Delacourte A, Fischer D F, Pollet D, De Strooper B, Merchiers P (2009). The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide generation in neurons. Science, 323(5916): 946–951
CrossRef Pubmed Google scholar
[72]
Tian L, Wu X, Chi C, Han M, Xu T, Zhuang Y (2008). ADAM10 is essential for proteolytic activation of Notch during thymocyte development. Int Immunol, 20(9): 1181–1187
CrossRef Pubmed Google scholar
[73]
Vassar R, Bennett B D, Babu-Khan S, Kahn S, Mendiaz E A, Denis P, Teplow D B, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski M A, Biere A L, Curran E, Burgess T, Louis J C, Collins F, Treanor J, Rogers G, Citron M (1999). Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science, 286(5440): 735–741
CrossRef Pubmed Google scholar
[74]
Watanabe N, Tomita T, Sato C, Kitamura T, Morohashi Y, Iwatsubo T (2005). Pen-2 is incorporated into the gamma-secretase complex through binding to transmembrane domain 4 of presenilin 1. J Biol Chem, 280(51): 41967–41975
CrossRef Pubmed Google scholar
[75]
Wyss-Coray T (2006). Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med, 12(9): 1005–1015
Pubmed

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