Role of Glutamate and NMDA Receptors in Alzheimer's Disease.
Excitatory glutamatergic neurotransmission via N-methyl-d-aspartate receptor (NMDAR) is critical for synaptic plasticity and survival of neurons. However, excessive NMDAR activity causes excitotoxicity and promotes cell death, underlying a potential mechanism of neurodegeneration occurred in Alzheimer's disease (AD). Studies indicate that the distinct outcomes of NMDAR-mediated responses are induced by regionalized receptor activities, followed by different downstream signaling pathways. The activation of synaptic NMDARs initiates plasticity and stimulates cell survival. In contrast, the activation of extrasynaptic NMDARs promotes cell death and thus contributes to the etiology of AD, which can be blocked by an AD drug, memantine, an NMDAR antagonist that selectively blocks the function of extrasynaptic NMDARs.
Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Rui
R
Wang
Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, USA.|Cell Biology & Biochemistry Department, Texas Tech University Health Sciences Center, Lubbock, TX, USA.|Neuroscience & Pharmacology Department, Texas Tech University Health Sciences Center, Lubbock, TX, USA.|Neurology Department, Texas Tech University Health Sciences Center, Lubbock, TX, USA.|Speech, Language and Hearing Sciences Departments, Texas Tech University Health Sciences Center, Lubbock, TX, USA.|Garrison Institute on Aging, South West Campus, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
P Hemachandra
PH
Reddy
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate
Alzheimer’s disease; NMDA receptors; excitotoxicity; extrasynaptic NMDA receptors; glutamate; memantine
Neurosci Lett. 2004 Aug 19;366(3):320-5
15288443
Nature. 1991 Oct 31;353(6347):844-6
1944558
Brain Res. 1986 Dec 3;399(1):156-61
2879613
Ann Neurol. 1996 Nov;40(5):759-66
8957017
Annu Rev Neurosci. 1988;11:61-80
2452598
Ann Neurol. 1986 Feb;19(2):105-11
2421636
Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9854-9
19482936
Neurobiol Dis. 2004 Apr;15(3):580-9
15056466
Neuroreport. 2014 Nov 12;25(16):1281-8
25275636
Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1977-81
8446617
Can J Neurol Sci. 2012 Jul;39(4):436-45
22728850
Ann Neurol. 1987 Apr;21(4):331-6
3579218
Neurosci Lett. 1989 Jun 5;101(1):62-6
2570384
J Neurosci. 2000 Jan 1;20(1):22-33
10627577
Mt Sinai J Med. 2010 Jan-Feb;77(1):32-42
20101720
Prog Neurobiol. 2001 Sep;65(1):1-105
11369436
Trends Pharmacol Sci. 1990 Jul;11(7):290-6
2167544
J Neurosci. 1987 Feb;7(2):369-79
2880938
Science. 1999 Jan 1;283(5398):70-4
9872743
FASEB J. 2008 Dec;22(12):4258-71
18711223
J Neurosci. 1993 May;13(5):2085-104
8097530
Neuropharmacology. 2009 Jan;56(1):2-5
18655795
Cell. 2012 Aug 3;150(3):633-46
22863013
J Neurochem. 2006 Aug;98(3):939-50
16893425
Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):E2518-27
23776240
J Neurochem. 2001 Jul;78(1):175-82
11432984
J Neurosci. 2007 Oct 31;27(44):11832-7
17978019
Prog Neurobiol. 1990;35(4):245-96
1980745
J Neurobiol. 1992 Nov;23(9):1261-76
1361523
Neuron. 2006 Dec 7;52(5):831-43
17145504
Nature. 1991 Feb 21;349(6311):704-6
1671712
Cell Calcium. 2010 Mar;47(3):264-72
20061018
Neurobiol Aging. 2011 Mar;32(3):553.e1-11
20416976
Brain Res. 1991 May 10;548(1-2):318-21
1678302
Nat Neurosci. 2005 Aug;8(8):1051-8
16025111
Science. 1991 Oct 4;254(5028):97-9
1925564
Brain Res. 1997 Apr 18;754(1-2):65-71
9134960
Neurotox Res. 2000;2(2-3):85-97
16787834
J Neurosci. 2007 Jan 24;27(4):796-807
17251419
J Biol Chem. 2007 Apr 13;282(15):11590-601
17308309
Curr Top Med Chem. 2006;6(8):787-99
16719817
Eur J Neurosci. 2000 Sep;12(9):3117-23
10998095
Int J Geriatr Psychiatry. 2003 Sep;18(Suppl 1):S23-32
12973747
Nat Rev Neurosci. 2010 Oct;11(10):682-96
20842175
Cold Spring Harb Perspect Biol. 2012 Jun 01;4(6):null
22510460
N Engl J Med. 1994 Mar 3;330(9):613-22
7905600
J Neurosci. 2008 Dec 31;28(53):14486-91
19118183
Neuron. 1988 Oct;1(8):623-34
2908446
J Neurosci Res. 1995 Jul 1;41(4):561-6
7473888
Brain Res. 1995 Jul 17;686(1):49-60
7583271
J Neurosci. 2007 Mar 14;27(11):2866-75
17360908
J Neuroinflammation. 2004 Apr 20;1(1):2
15285800
Neurochem Int. 2007 May;50(6):872-80
17403555
Neuron. 2003 Mar 27;37(6):925-37
12670422
J Neurochem. 1984 Jan;42(1):1-11
6139418
Nature. 1992 Dec 3;360(6403):471-4
1448171
J Clin Psychiatry. 2006;67 Suppl 3:3-7; quiz 23
16649845
Nat Neurosci. 2009 Dec;12(12):1567-76
19935655
Biochem Soc Trans. 2006 Nov;34(Pt 5):936-8
17052231
Science. 1993 Aug 13;261(5123):921-3
8346443
BMJ. 2009 Feb 05;338:b158
19196745
J Neurosci Res. 2008 Mar;86(4):845-60
17969100
Cell Calcium. 2011 Mar;49(3):184-90
21349580
Science. 1992 Oct 23;258(5082):668-71
1411576
Nat Neurosci. 2002 May;5(5):405-14
11953750
Int J Geriatr Psychiatry. 2003 Sep;18(Suppl 1):S33-40
12973748
J Neuropathol Exp Neurol. 1997 Aug;56(8):901-11
9258260
Science. 1992 Nov 27;258(5087):1498-501
1359647
Behav Brain Res. 2003 Mar 18;140(1-2):1-47
12644276
J Neurosci. 1988 Jan;8(1):185-96
2892896
Science. 1995 Aug 18;269(5226):973-7
7638622
Neuron. 2014 Apr 16;82(2):279-93
24742457