Towards retinoid therapy for Alzheimer's disease

Current Alzheimer Research

Volumn 6, Issue 3, 2009, Pages 302-311

  Shudo, K ^b   Fukasawa, H ^a   Nakagomi, M ^b   Yamagata, N ^b  

^a Institute of Medicinal Molecular Design Inc   (Japan)

^b Kawasaki   (Japan)

Author keywords

Alzheimer's disease; Immunology; Inflammation; Neurodegeneration; Regulatory T cell; Retinoic acid receptors; Retinoid

Indexed keywords

ALITRETINOIN; AMYLOID BETA PROTEIN; CYCLOOXYGENASE 2 INHIBITOR; ETRETINATE; NONSTEROID ANTIINFLAMMATORY AGENT; PREALBUMIN; RETINOIC ACID; RETINOIC ACID RECEPTOR; RETINOID; RETINOID X RECEPTOR; RETINOL; TAMIBAROTENE;

ALZHEIMER DISEASE; ANTIINFLAMMATORY ACTIVITY; ATHEROSCLEROSIS; AUTOIMMUNE DISEASE; CELL REGENERATION; CHOLINERGIC TRANSMISSION; CROHN DISEASE; DRUG EFFECT; HUMAN; IMMUNOPATHOGENESIS; IN-STENT RESTENOSIS; INFECTION; INSULIN DEPENDENT DIABETES MELLITUS; LEARNING; LYMPHOCYTE DIFFERENTIATION; MEMORY; MEMORY DISORDER; NERVE CELL; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROMYELOCYTIC LEUKEMIA; PSORIASIS; REVIEW; RHEUMATOID ARTHRITIS; SJOEGREN SYNDROME; TREATMENT OUTCOME;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; ANIMALS; ANTIPSYCHOTIC AGENTS; AUTOIMMUNE DISEASES; CELL DIFFERENTIATION; HUMANS; INFLAMMATION; LEARNING; MODELS, BIOLOGICAL; RECEPTORS, RETINOIC ACID; RETINOIDS; T-LYMPHOCYTES;

EID: 67149115541     PISSN: 15672050     EISSN: None     Source Type: Journal    
DOI: 10.2174/156720509788486581     Document Type: Review

References (160)

1. Cummings JL. Alzheimer's disease. N Engl J Med 351: 56-67 (2004). (Pubitemid 38857248)
2. Roberson ED, Mucke L. 100 years and counting: prospects for defeating Alzheimer's disease. Science 314: 781-784 (2006). (Pubitemid 44706637)
3. Hardy J. A hundred years of Alzheimer's disease research. Neuron 52: 3-13 (2006). (Pubitemid 44472602)
4. Sporn MB, Roberts AB, Goodman AB, Eds. The Retinoids. ACADEMIC PRESS, INC. 1(2): (1984).
5. Dawson MI, Okamura WH, Eds. Chemistry and Biology of Synthetic Retinoids. CRC Press, Inc. (1990).
6. Nau H, Blaner WS, Eds. Retinoids: The biochemical and molecular basis of vitamin A and retinoid action. Springer (1999).
7. Kagechika H, Shudo K. Synthetic retinoids: recent developments concerning structure and clinical utility. J Med Chem 48: 5875-5883 (2005). (Pubitemid 41324597)
8. Kagechika H. Novel synthetic retinoids and separation of the pleiotropic retinoidal activities. Curr Med Chem 9: 591-608 (2002). (Pubitemid 34436436)
9. Dawson MI. Synthetic retinoids and their nuclear receptors. Curr Med Chem Anticancer Agents 4: 199-230 (2004). (Pubitemid 38647583)
10. de Lera AR, Bourguet W, Altucci L, Gronemeyer H. Design of selective nuclear receptor modulators: RAR and RXR as a case study. Nat Rev Drug Discov 6: 811-820 (2007). (Pubitemid 47504872)
11. Napoli JL. Retinoic acid: its biosynthesis and metabolism. Prog Nucleic Acid Res Mol Biol 63: 139-188 (1999).
12. Ross AC. Retinoid production and catabolism: role of diet in regulating retinol esterification and retinoic Acid oxidation. J Nutr 133: 291S-296S (2003). (Pubitemid 36070621)
13. Blomhoff R, Blomhoff HK. Overview of retinoid metabolism and function. J Neurobiol 66: 606-630 (2006). (Pubitemid 43941649)
14. Germain P, Chambon P, Eichele G, Evans RM, Lazar MA, Leid M, et al. International Union of Pharmacology. LX. Retinoic acid receptors. Pharmacol Rev 58: 712-725 (2006).
15. Balmer JE, Blomhoff R. Gene expression regulation by retinoic acid. J Lipid Res 43: 1773 - 1808 (2002). (Pubitemid 35315797)
16. Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood 111: 2505-2515 (2008).
17. Miwako I, Kagechika H. Tamibarotene. Drugs Today (Barc) 43: 563-568 (2007).
18. Altucci L, Leibowitz MD, Ogilvie KM, de Lera AR, Gronemeyer H. RAR and RXR modulation in cancer and metabolic disease. Nat Rev Drug Discov 6: 793-810 (2007). (Pubitemid 47504871)
19. Oikawa T, Okayasu I, Ashino H, Morita I, Murota S, Shudo K. Three novel synthetic retinoids, Re 80, Am 580 and Am 80, all exhibit anti-angiogenic activity in vivo. Eur J Pharmacol 249: 113-116 (1993). (Pubitemid 23326917)
20. Sardana K, Sehgal VN. Retinoids: fascinating up-and-coming scenario. J Dermatol 30: 355-380 (2003).
21. Ishibashi Y. Clinical Effect of Am-80 Ointment on Psoriasis and Pustulosis Palmaris et Plantaris (Phase III Study). RinshouIyaku 11: 747-759 (1995).
22. Nickoloff BJ. Cracking the cytokine code in psoriasis. Nat Med 13: 242-244 (2007). (Pubitemid 46376653)
23. Kuwabara K, Shudo K, Hori Y. Novel synthetic retinoic acid inhibits rat collagen arthritis and differentially affects serum immunoglobulin subclass levels. FEBS Lett 378: 153-156 (1996). (Pubitemid 26015564)
24. Nagai H, Matsuura S, Bouda K, Takaoka Y, Wang T, Niwa S, et al. Effect of Am-80, a synthetic derivative of retinoid, on experimental arthritis in mice. Pharmacology 58: 101-112 (1999).
25. Beehler BC, Brinckerhoff CE, Ostrowski J. Selective retinoic acid receptor ligands for rheumatoid arthritis. Curr Opin Investig Drugs 5: 1153-1157 (2004). (Pubitemid 39545283)
26. Wiegman PJ, Barry WL, McPherson JA, McNamara CA, Gimple LW, Sanders JM, et al. All-trans-retinoic acid limits restenosis after balloon angioplasty in the focally atherosclerotic rabbit : A favorable effect on vessel remodeling. Arterioscler Thromb Vasc Biol 20: 89-95 (2000).
27. Fujiu K, Manabe I, Ishihara A, Oishi Y, Iwata H, Nishimura G, et al. Synthetic retinoid Am80 suppresses smooth muscle phenotypic modulation and in-stent neointima formation by inhibiting KLF5. Circ Res 97: 1132-1141 (2005).
28. Sato M, Shudo K, Hiragun A. Functional studies of newly synthesized benzoic acid derivatives: identification of highly potent retinoid-like activity. J Cell Physiol 135: 179-188 (1988). (Pubitemid 18143540)
29. Massaro GD, Massaro D. Retinoic acid treatment abrogates elastase- induced pulmonary emphysema in rats. Nat Med 3: 675-677 (1997). (Pubitemid 27264979)
30. Nishikiori N, Osanai M, Chiba H, Kojima T, Mitamura Y, Ohguro H, et al. Glial cell-derived cytokines attenuate the breakdown of vascular integrity in diabetic retinopathy. Diabetes 56: 1333-1340 (2007).
31. Nishikiori N, Osanai M, Chiba H, Kojima T, Ohguro H, Sawada N. Inhibitory effects of retinoic acid receptor alpha stimulants on murine cataractogenesis through suppression of deregulated calpains. Invest Ophthalmol Vis Sci 48: 2224-2229 (2007). (Pubitemid 351261298)
32. Miwako I, Shudo K. Oral administration of synthetic retinoid Am80 inhibits the development of type 1 diabetes in NOD mice. Biol Pharm Bull (in press).
33. Osanai M, Nishikiori N, Murata M, Chiba H, Kojima T, Sawada N. Cellular retinoic acid bioavailability determines epithelial integrity: Role of retinoic acid receptor alpha agonists in colitis. Mol Pharmacol 71: 250-258 (2007). (Pubitemid 46020995)
34. Phase II Study of RR110 in Patients with Active Crohn's Disease [online]. Available from URL: http://clinicaltrials.gov/ct2/show/NCT00417391 [Accessed 2008 July 7]
35. Standeven AM, Teng M, Chandraratna RA. Lack of involvement of retinoic acid receptor alpha in retinoid-induced skin irritation in hairless mice. Toxicol Lett 92: 231-240 (1997). (Pubitemid 27400114)
36. Iulianella A, Lohnes D. Contribution of retinoic acid receptor gamma to retinoid-induced craniofacial and axial defects. Dev Dyn 209: 92-104 (1997). (Pubitemid 27188342)
37. Look J, Landwehr J, Bauer F, Hoffmann AS, Bluethmann H, LeMotte P. Marked resistance of RAR gamma-deficient mice to the toxic effects of retinoic acid. Am J Physiol 269: E91-98 (1995).
38. Reczek PR, Ostrowski J, Yu KL, Chen S, Hammer L, Roalsvig T, et al. Role of retinoic acid receptor gamma in the Rhino mouse and rabbit irritation models of retinoid activity. Skin Pharmacol 8: 292-299 (1995).
39. Seabrook GR, Ray WJ, Shearman M, Hutton M. Beyond amyloid: the next generation of Alzheimer's disease therapeutics. Mol Interv 7: 261-270 (2007). (Pubitemid 47607486)
40. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, et al. Inflammation and Alzheimer's disease. Neurobiol Aging 21: 383-421 (2000).
41. Britschgi M, Wyss-Coray T. Immune cells may fend off Alzheimer disease. Nat Med 13: 408-409 (2007). (Pubitemid 46559817)
42. Maden M, Hind M. Retinoic acid, a regeneration-inducing molecule. Dev Dyn 226: 237-244 (2003). (Pubitemid 36158168)
43. Maden M. Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat Rev Neurosci 8: 755-765 (2007). (Pubitemid 47462115)
44. Misner DL, Jacobs S, Shimizu Y, de Urquiza AM, Solomin L, Perlmann T, et al. Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity. Proc Natl Acad Sci USA 98: 11714-11719 (2001).
45. Mingaud F, Mormede C, Etchamendy N, Mons N, Niedergang B, Wietrzych M, et al. Retinoid hyposignaling contributes to aging-related decline in hippocampal function in short-term/working memory organization and long-term declarative memory encoding in mice. J Neurosci 28: 279-291 (2008).
46. Goodman AB, Pardee AB. Evidence for defective retinoid transport and function in late onset Alzheimer's disease. Proc Natl Acad Sci USA 100: 2901-2905 (2003). (Pubitemid 36297596)
47. Goodman AB. Retinoid receptors, transporters, and metabolizers as therapeutic targets in late onset Alzheimer disease. J Cell Physiol 209: 598-603 (2006). (Pubitemid 44665675)
48. Weiner HL, Frenkel D. Immunology and immunotherapy of Alzheimer's disease. Nat Rev Immunol 6: 404-416 (2006).
49. Prinzen C, Muller U, Endres K, Fahrenholz F, Postina R. Genomic structure and functional characterization of the human ADAM10 promoter. FASEB J 19: 1522-1524 (2005). (Pubitemid 41279018)
50. Fahrenholz F, Postina R. Alpha-secretase activation - an approach to Alzheimer's disease therapy. Neurodegener Dis 3: 255-261 (2006). (Pubitemid 44600312)
51. Fahrenholz F. Alpha-secretase as a therapeutic target. Curr Alzheimer Res 4: 412-417 (2007). (Pubitemid 47416634)
52. Husson M, Enderlin V, Delacourte A, Ghenimi N, Alfos S, Pallet V, et al. Retinoic acid normalizes nuclear receptor mediated hypoexpression of proteins involved in beta-amyloid deposits in the cerebral cortex of vitamin A deprived rats. Neurobiol Dis 23: 1-10 (2006).
53. Corcoran JP, So PL, Maden M. Disruption of the retinoid signalling pathway causes a deposition of amyloid beta in the adult rat brain. Eur J Neurosci 20: 896-902 (2004). (Pubitemid 39141297)
54. El Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C, et al. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 13: 432-438 (2007).
55. Beers DR, Henkel JS, Zhao W, Wang J, Appel SH. CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proc Natl Acad Sci USA 105: 15558-15563 (2008).
56. Huang H, Patel DD, Manton KG. The immune system in aging: roles of cytokines, T cells and NK cells. Front Biosci 10: 192-215 (2005).
57. Lucas SM, Rothwell NJ, Gibson RM. The role of inflammation in CNS injury and disease. Br J Pharmacol 147 (Suppl 1): S232-240 (2006). (Pubitemid 43077281)
58. Weisman D, Hakimian E, Ho GJ. Interleukins, inflammation, and mechanisms of Alzheimer's disease. Vitam Horm 74: 505-530 (2006).
59. Gadient RA, Otten U. Identification of interleukin-6 (IL-6)- expressing neurons in the cerebellum and hippocampus of normal adult rats. Neurosci Lett 182: 243-246 (1994). (Pubitemid 24380247)
60. Tehranian R, Hasanvan H, Iverfeldt K, Post C, Schultzberg M. Early induction of interleukin-6 mRNA in the hippocampus and cortex of APPsw transgenic mice Tg2576. Neurosci Lett 301: 54-58 (2001). (Pubitemid 32182393)
61. Bhojak TJ, DeKosky ST, Ganguli M, Kamboh MI. Genetic polymorphisms in the cathespin D and interleukin-6 genes and the risk of Alzheimer's disease. Neurosci Lett 288: 21-24 (2000). (Pubitemid 30408429)
62. Shibata N, Ohnuma T, Takahashi T, Baba H, Ishizuka T, Ohtsuka M, et al. Effect of IL-6 polymorphism on risk of Alzheimer disease: genotype-phenotype association study in Japanese cases. Am J Med Genet 114: 436-439 (2002).
63. Zitnik RJ, Kotloff RM, Latifpour J, Zheng T, Whiting NL, Schwalb J, et al. Retinoic acid inhibition of IL-1-induced IL-6 production by human lung fibroblasts. J Immunol 152: 1419-1427 (1994).
64. Kagechika H, Kawachi E, Fukasawa H, Saito G, Iwanami N, Umemiya H, et al. Inhibition of IL-1-induced IL-6 production by synthetic retinoids. Biochem Biophys Res Commun 231: 243-248 (1997).
65. Dheen ST, Jun Y, Yan Z, Tay SS, Ling EA. Retinoic acid inhibits expression of TNF-alpha and iNOS in activated rat microglia. Glia 50: 21-31 (2005). (Pubitemid 40516817)
66. Kaur C, Sivakumar V, Dheen ST, Ling EA. Insulin-like growth factor I and II expression and modulation in amoeboid microglial cells by lipopolysaccharide and retinoic acid. Neuroscience 138: 1233-1244 (2006). (Pubitemid 43363541)
67. Schwab C, McGeer PL. Inflammatory aspects of Alzheimer disease and other neurodegenerative disorders. J Alzheimers Dis 13: 359-369 (2008). (Pubitemid 352039027)
68. Hyman BT, Smith C, Buldyrev I, Whelan C, Brown H, Tang MX, et al. Autoantibodies to amyloid-beta and Alzheimer's disease. Ann Neurol 49: 808-810 (2001).
69. Troost D, van den Oord JJ, de Jong JM, Swaab DF. Lymphocytic infiltration in the spinal cord of patients with amyotrophic lateral sclerosis. Clin Neuropathol 8: 289-294 (1989). (Pubitemid 20101117)
70. Kawamata T, Akiyama H, Yamada T, McGeer PL. Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am J Pathol 140: 691-707 (1992).
71. Yoshino H. Immunological aspects of amyotrophic lateral sclerosis. Nippon Rinsho 52: 2984-2989 (1994).
72. Hunot S, Hirsch EC. Neuroinflammatory processes in Parkinson's disease. Ann Neurol 53 (Suppl 3): S49-58; discussion S58-60 (2003). (Pubitemid 36368562)
73. McGeachy MJ, Cua DJ. Th17 cell differentiation: the long and winding road. Immunity 28: 445-453 (2008).
74. Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28: 454-467 (2008).
75. Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M, et al. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med 13: 1173-1175 (2007).
76. Wang W, Milani M, Ostlie N, Okita D, Agarwal RK, Caspi RR, et al. C57BL/6 mice genetically deficient in IL-12/IL-23 and IFNgamma are susceptible to experimental autoimmune myasthenia gravis, suggesting a pathogenic role of non-Th1 cells. J Immunol 178: 7072-7080 (2007).
77. Ifergan I, Kebir H, Bernard M, Wosik K, Dodelet-Devillers A, Cayrol R, et al. The blood-brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells. Brain 131: 785-799 (2008).
78. Zhong Z, Deane R, Ali Z, Parisi M, Shapovalov Y, O'Banion MK, et al. ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration. Nat Neurosci 11: 420-422 (2008).
79. Racke MK, Burnett D, Pak SH, Albert PS, Cannella B, Raine CS, et al. Retinoid treatment of experimental allergic encephalomyelitis. IL-4 production correlates with improved disease course. J Immunol 154: 450-458 (1995).
80. Wang T, Niwa S, Bouda K, Matsuura S, Homma T, Shudo K, et al. The effect of Am-80, one of retinoid derivatives on experimental allergic encephalomyelitis in rats. Life Sci 67: 1869-1879 (2000).
81. Miyagawa N, Homma T, Kagechika H, Shudo K, Nagai H. Effect of synthetic retinoid, TAC-101, on experimental autoimmune disease. Pharmacology 67: 21-31 (2003). (Pubitemid 35356783)
82. Iwata M, Eshima Y, Kagechika H. Retinoic acids exert direct effects on T cells to suppress Th1 development and enhance Th2 development via retinoic acid receptors. Int Immunol 15: 1017-1025 (2003). (Pubitemid 36987299)
83. Fukasawa H, Kagechika H, Shudo K. Retinoid therapy for autoimmune diseases. Jpn J Clin Immunol 29: 114-126 (2006).
84. Ivanov, II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126: 1121-1133 (2006).
85. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155: 1151-1164 (1995).
86. Tang Q, Bluestone JA. The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat Immunol 9: 239-244 (2008). (Pubitemid 351267321)
87. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4: 330-336 (2003).
88. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057-1061 (2003). (Pubitemid 36222930)
89. Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199: 971-979 (2004). (Pubitemid 38481088)
90. Balandina A, Lecart S, Dartevelle P, Saoudi A, Berrih-Aknin S. Functional defect of regulatory CD4(+)CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis. Blood 105: 735-741 (2005). (Pubitemid 40070760)
91. Yamano Y, Takenouchi N, Li HC, Tomaru U, Yao K, Grant CW, et al. Virus-induced dysfunction of CD4+CD25+ T cells in patients with HTLV-I-associated neuroimmunological disease. J Clin Invest 115: 1361-1368 (2005).
92. Rosenkranz D, Weyer S, Tolosa E, Gaenslen A, Berg D, Leyhe T, et al. Higher frequency of regulatory T cells in the elderly and increased suppressive activity in neurodegeneration. J Neuroimmunol 188: 117-127 (2007).
93. Reynolds AD, Banerjee R, Liu J, Gendelman HE, Mosley RL. Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease. J Leukoc Biol 82: 1083-1094 (2007). (Pubitemid 350133504)
94. Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, et al. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317: 256-260 (2007).
95. Coombes JL, Siddiqui KR, Arancibia-Carcamo CV, Hall J, Sun CM, Belkaid Y, et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med 204: 1757-1764 (2007).
96. Kang SG, Lim HW, Andrisani OM, Broxmeyer HE, Kim CH. Vitamin A metabolites induce gut-homing Foxp3+ regulatory T cells. J Immunol 179: 3724-3733 (2007).
97. Elias KM, Laurence A, Davidson TS, Stephens G, Kanno Y, Shevach EM, et al. Retinoic acid inhibits Th17 polarization and enhances Foxp3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood 111: 1013-1020 (2008).
98. Benson MJ, Pino-Lagos K, Rosemblatt M, Noelle RJ. All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J Exp Med 204: 1765-1774 (2007). (Pubitemid 47236315)
99. Sun CM, Hall JA, Blank RB, Bouladoux N, Oukka M, Mora JR, et al. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 204: 1775-1785 (2007).
100. Kim CH. Regulation of Foxp3 regulatory T cells and Th17 cells by retinoids. Clin Dev Immunol: 1-12 (2008). (Pubitemid 351712880)
101. Takaki H, Ichiyama K, Koga K, Chinen T, Takaesu G, Sugiyama Y, et al. STAT6 Inhibits TGF-beta1-mediated Foxp3 induction through direct binding to the Foxp3 promoter, which is reverted by retinoic acid receptor. J Biol Chem 283: 14955-14962 (2008).
102. Schambach F, Schupp M, Lazar MA, Reiner SL. Activation of retinoic acid receptor-alpha favours regulatory T cell induction at the expense of IL-17-secreting T helper cell differentiation. Eur J Immunol 37: 2396-2399 (2007). (Pubitemid 47423609)
103. von Boehmer H. Oral tolerance: is it all retinoic acid? J Exp Med 204: 1737-1739 (2007).
104. Strandberg TE, Pitkala KH, Linnavuori K, Tilvis RS. Cognitive impairment and infectious burden in the elderly. Arch Gerontol Geriatr Suppl: 419-423 (2004). (Pubitemid 38822894)
105. D'Andrea MR. Add Alzheimer's disease to the list of autoimmune diseases. Med Hypotheses 64: 458-463 (2005). (Pubitemid 40023001)
106. Perry VH, Cunningham C, Holmes C. Systemic infections and inflammation affect chronic neurodegeneration. Nat Rev Immunol 7: 161-167 (2007). (Pubitemid 46174862)
107. Miklossy J. Chronic inflammation and amyloidogenesis in Alzheimer's disease - role of spirochetes. J Alzheimers Dis 13: 381-391 (2008). (Pubitemid 352039022)
108. Itzhaki RF, Wozniak MA. Herpes simplex virus type 1 in Alzheimer's disease: the enemy within. J Alzheimers Dis 13: 393-405 (2008). (Pubitemid 352039023)
109. Balin BJ, Little CS, Hammond CJ, Appelt DM, Whittum-Hudson JA, Gerard HC, et al. Chlamydophila pneumoniae and the etiology of late-onset Alzheimer's disease. J Alzheimers Dis 13: 371-380 (2008).
110. Nicolson GL, Nasralla MY, Haier J, Pomfret J. High frequency of systemic mycoplasmal infections in Gulf War veterans and civilians with Amyotrophic Lateral Sclerosis (ALS). J Clin Neurosci 9: 525-529 (2002).
111. Doty RL. The olfactory vector hypothesis of neurodegenerative disease: is it viable? Ann Neurol 63: 7-15 (2008).
112. Ross GW, Petrovitch H, Abbott RD, Tanner CM, Popper J, Masaki K, et al. Association of olfactory dysfunction with risk for future Parkinson's disease. Ann Neurol 63: 167-173 (2008).
113. Tabert MH, Liu X, Doty RL, Serby M, Zamora D, Pelton GH, et al. A 10-item smell identification scale related to risk for Alzheimer's disease. Ann Neurol 58: 155-160 (2005).
114. Rawson NE, LaMantia AS. Once and again: retinoic acid signaling in the developing and regenerating olfactory pathway. J Neurobiol 66: 653-676 (2006). (Pubitemid 43941650)
115. Rawson NE, LaMantia AS. A speculative essay on retinoic acid regulation of neural stem cells in the developing and aging olfactory system. Exp Gerontol 42: 46-53 (2007). (Pubitemid 44937824)
116. Mey J, Morassutti DJ, Brook G, Liu RH, Zhang YP, Koopmans G, et al. Retinoic acid synthesis by a population of NG2-positive cells in the injured spinal cord. Eur J Neurosci 21: 1555-1568 (2005).
117. Mey J. New therapeutic target for CNS injury? The role of retinoic acid signaling after nerve lesions. J Neurobiol 66: 757-779 (2006). (Pubitemid 43939198)
118. Kern J, Schrage K, Koopmans GC, Joosten EA, McCaffery P, Mey J. Characterization of retinaldehyde dehydrogenase-2 induction in NG2-positive glia after spinal cord contusion injury. Int J Dev Neurosci 25: 7-16 (2007). (Pubitemid 46162067)
119. Zhelyaznik N, Mey J. Regulation of retinoic acid receptors alpha, beta and retinoid X receptor alpha after sciatic nerve injury. Neuroscience 141: 1761-1774 (2006). (Pubitemid 44233131)
120. Mey J, Schrage K, Wessels I, Vollpracht-Crijns I. Effects of inflammatory cytokines IL-1beta, IL-6, and TNFalpha on the intracellular localization of retinoid receptors in Schwann cells. Glia 55: 152-164 (2007).
121. Vergara MN, Arsenijevic Y, Del Rio-Tsonis K. CNS regeneration: a morphogen's tale. J Neurobiol 64: 491-507 (2005). (Pubitemid 41114055)
122. Strickland S, Mahdavi V. The induction of differentiation in teratocarcinoma stem cells by retinoic acid. Cell 15: 393-403 (1978). (Pubitemid 9052408)
123. Kuff EL, Fewell JW. Induction of neural-like cells and acetylcholinesterase activity in cultures of F9 teratocarcinoma treated with retinoic acid and dibutyryl cyclic adenosine monophosphate. Dev Biol 77: 103-115 (1980). (Pubitemid 10054919)
124. Liesi P, Rechardt L, Wartiovaara J. Nerve growth factor induces adrenergic neuronal differentiation in F9 teratocarcinoma cells. Nature 306: 265-267 (1983). (Pubitemid 14232355)
125. McBurney MW, Jones-Villeneuve EM, Edwards MK, Anderson PJ. Control of muscle and neuronal differentiation in a cultured embryonal carcinoma cell line. Nature 299: 165-167 (1982). (Pubitemid 12056794)
126. Maden M. Retinoids and spinal cord development. J Neurobiol 66: 726-738 (2006).
127. Krezel W, Kastner P, Chambon P. Differential expression of retinoid receptors in the adult mouse central nervous system. Neuroscience 89: 1291-1300 (1999). (Pubitemid 29074646)
128. Wong LF, Yip PK, Battaglia A, Grist J, Corcoran J, Maden M, et al. Retinoic acid receptor beta2 promotes functional regeneration of sensory axons in the spinal cord. Nat Neurosci 9: 243-250 (2006).
129. Corcoran J, So PL, Barber RD, Vincent KJ, Mazarakis ND, Mitrophanous KA, et al. Retinoic acid receptor beta2 and neurite outgrowth in the adult mouse spinal cord in vitro. J Cell Sci 115: 3779-3786 (2002). (Pubitemid 35203604)
130. Wallen-Mackenzie A, Mata de Urquiza A, Petersson S, Rodriguez FJ, Friling S, Wagner J, et al. Nurr1-RXR heterodimers mediate RXR ligand-induced signaling in neuronal cells. Genes Dev 17: 3036-3047 (2003).
131. Heneka MT, Landreth GE. PPARs in the brain. Biochim Biophys Acta 1771: 1031-1045 (2007). (Pubitemid 47208548)
132. Malaspina A, Turkheimer F. A review of the functional role and of the expression profile of retinoid signaling and of nuclear receptors in human spinal cord. Brain Res Bull 71: 437-446 (2007). (Pubitemid 46157165)
133. Kobayashi M, Matsuoka I, Kurihara K. Cholinergic differentiation of cultured sympathetic neurons induced by retinoic acid. Induction of choline acetyltransferase-mRNA and suppression of tyrosine hydroxylase-mRNA levels. FEBS Lett 337: 259-264 (1994).
134. Pedersen WA, Berse B, Schuler U, Wainer BH, Blusztajn JK. Alltrans- and 9-cis-retinoic acid enhance the cholinergic properties of a murine septal cell line: evidence that the effects are mediated by activation of retinoic acid receptor-alpha. J Neurochem 65: 50-58 (1995).
135. Berse B, Blusztajn JK. Coordinated up-regulation of choline acetyltransferase and vesicular acetylcholine transporter gene expression by the retinoic acid receptor alpha, cAMP, and leukemia inhibitory factor/ciliary neurotrophic factor signaling pathways in a murine septal cell line. J Biol Chem 270: 22101-22104 (1995).
136. Shudo K, Kagechika H, Yamazaki N, Igarashi M, Tateda C. A synthetic retinoid Am80 (tamibarotene) rescues the memory deficit caused by scopolamine in a passive avoidance paradigm. Biol Pharm Bull 27: 1887-1889 (2004). (Pubitemid 41701625)
137. Samad TA, Krezel W, Chambon P, Borrelli E. Regulation of dopaminergic pathways by retinoids: activation of the D2 receptor promoter by members of the retinoic acid receptor-retinoid X receptor family. Proc Natl Acad Sci USA 94: 14349-14354 (1997). (Pubitemid 28041376)
138. Lane MA, Bailey SJ. Role of retinoid signalling in the adult brain. Prog Neurobiol 75: 275-293 (2005). (Pubitemid 40693128)
139. Chiang MY, Misner D, Kempermann G, Schikorski T, Giguere V, Sucov HM, et al. An essential role for retinoid receptors RARbeta and RXRgamma in long-term potentiation and depression. Neuron 21: 1353-1361 (1998).
140. Etchamendy N, Enderlin V, Marighetto A, Vouimba RM, Pallet V, Jaffard R, et al. Alleviation of a selective age-related relational memory deficit in mice by pharmacologically induced normalization of brain retinoid signaling. J Neurosci 21: 6423-6429 (2001).
141. Etchamendy N, Enderlin V, Marighetto A, Pallet V, Higueret P, Jaffard R. Vitamin A deficiency and relational memory deficit in adult mice: relationships with changes in brain retinoid signalling. Behav Brain Res 145: 37-49 (2003). (Pubitemid 37188631)
142. Lucarelli E, Kaplan DR, Thiele CJ. Selective regulation of TrkA and TrkB receptors by retinoic acid and interferon-gamma in human neuroblastoma cell lines. J Biol Chem 270: 24725-24731 (1995).
143. Bulens F, Ibanez-Tallon I, Van Acker P, De Vriese A, Nelles L, Belayew A, et al. Retinoic acid induction of human tissue-type plasminogen activator gene expression via a direct repeat element (DR5) located at -7 kilobases. J Biol Chem 270: 7167-7175 (1995).
144. Melchor JP, Strickland S. Tissue plasminogen activator in central nervous system physiology and pathology. Thromb Haemost 93: 655-660 (2005). (Pubitemid 40485400)
145. Pang PT, Teng HK, Zaitsev E, Woo NT, Sakata K, Zhen S, et al. Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science 306: 487-491 (2004).
146. Brouillette J, Quirion R. Transthyretin: A key gene involved in the maintenance of memory capacities during aging. Neurobiol Aging 29: 1721-1732 (2008).
147. Monaco HL. The transthyretin-retinol-binding protein complex. Biochim Biophys Acta 1482: 65-72 (2000). (Pubitemid 30780029)
148. Merched A, Serot JM, Visvikis S, Aguillon D, Faure G, Siest G. Apolipoprotein E, transthyretin and actin in the CSF of Alzheimer's patients: relation with the senile plaques and cytoskeleton biochemistry. FEBS Lett 425: 225-228 (1998). (Pubitemid 28178895)
149. Schwarzman AL, Gregori L, Vitek MP, Lyubski S, Strittmatter WJ, Enghilde JJ, et al. Transthyretin sequesters amyloid beta protein and prevents amyloid formation. Proc Natl Acad Sci USA 91: 8368-8372 (1994).
150. Carro E, Trejo JL, Gomez-Isla T, LeRoith D, Torres-Aleman I. Serum insulin-like growth factor I regulates brain amyloid-beta levels. Nat Med 8: 1390-1397 (2002). (Pubitemid 36019424)
151. Kempermann G. Why new neurons? Possible functions for adult hippocampal neurogenesis. J Neurosci 22: 635-638 (2002). (Pubitemid 34141743)
152. Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, et al. Increased hippocampal neurogenesis in Alzheimer's disease. Proc Natl Acad Sci USA 101: 343-347 (2004).
153. Malaspina A, Michael-Titus AT. Is the modulation of retinoid and retinoid-associated signaling a future therapeutic strategy in neurological trauma and neurodegeneration? J Neurochem 104: 584-595 (2008).
154. Goodman AB. Three independent lines of evidence suggest retinoids as causal to schizophrenia. Proc Natl Acad Sci USA 95: 7240-7244 (1998). (Pubitemid 28293235)
155. Maret S, Franken P, Dauvilliers Y, Ghyselinck NB, Chambon P, Tafti M. Retinoic acid signaling affects cortical synchrony during sleep. Science 310: 111-113 (2005). (Pubitemid 41434547)
156. Sei H. Vitamin A and sleep regulation. J Med Invest 55: 1-8 (2008).
157. Bourhis E, Maheux J, Paquet B, Kagechika H, Shudo K, Rompre PP, et al. The transcription factors Nur77 and retinoid X receptors participate in amphetamine-induced locomotor activities. Psychopharmacology (Berl) 202: 635-648 (2009).
158. Levesque D, Rouillard C. Nur77 and retinoid X receptors: crucial factors in dopamine-related neuroadaptation. Trends Neurosci 30: 22-30 (2007). (Pubitemid 46001681)
159. Sporn MB, Harris ED, Jr. Proliferative diseases. Am J Med 70: 1231-1235 (1981). (Pubitemid 11072117)
160. Ding Y, Qiao A, Wang Z, Goodwin JS, Lee E-S, Block ML, et al. Retinoic acid attenuates β-amyloid deposition and resques memory deficits in an Alzheimer's disease transgenic mouse model. J Neurosci 28: 11622-11634 (2008).