11. Boissel J-P, Bros M, Schro ¨ck A, Go ¨dtelArmbrust U, Fo ¨rstermann U (2004) Cyclic
AMP-mediated upregulation of the expression
of neuronal NO synthase in human A673 neuroepithelioma cells results in a decrease in the
level of bioactive NO production: analysis of
the signaling mechanisms that are involved.
Biochemistry 43:7197–7206
12. Schulz JB, Matthews RT, Klockgether T,
Dichgans J, Beal MF (1997) The role of mitochondrial dysfunction and neuronal nitric
oxide in animal models of neurodegenerative
diseases. Mol Cell Biochem 174:193–197
13. Pou S, Keaton L, Surichamorn W, Rosen GM
(1999) Mechanism of superoxide generation
by neuronal nitric-oxide synthase. J Biol
Chem 274:9573–9580
14. Grotta J, Clark W, Coull B, Pettigrew LC,
Mackay B, Goldstein LB, Meissner I,
Murphy D, LaRue L (1995) Safety and tolerability of the glutamate antagonist CGS 19755
(selfotel) in patients with acute ischemic stroke:
results of a phase IIa randomized trial. Stroke
26:602–605
15. Sveinbjornsdottir S, Sander J, Upton D,
Thompson P, Patsalos P, Hirt D, Emre M,
Lowe D, Duncan JS (1993) The excitatory
amino acid antagonist D-CPP-ene (SDZ
EAA-494) in patients with epilepsy. Epilepsy
Res 16:165–174
16. Albers G, Atkinson R, Kelley R, Rosenbaum D
(1995) Safety, tolerability, and pharmacokinetics of the N-methyl-D-aspartate antagonist
dextrorphan in patients with acute stroke.
Stroke 26:254–258
17. Albers GW, Goldstein LB, Hall D, Lesko LM,
Investigators AAS (2001) Aptiganel hydrochloride in acute ischemic stroke: a randomized
controlled trial. JAMA 286:2673–2682
18. Hoyte L, Barber P, Buchan A, Hill M (2004)
The rise and fall of NMDA antagonists for
ischemic stroke. Curr Mol Med 4:131–136
19. De Keyser J, Sulter G, Luiten PG (1999) Clinical trials with neuroprotective drugs in acute
ischaemic stroke: are we doing the right thing?
Trends Neurosci 22:535–540
20. Aarts M, Liu Y, Liu L, Besshoh S, Arundine M,
Gurd JW, Wang YT, Salter MW, Tymianski M
(2002) Treatment of ischemic brain damage by
perturbing NMDA receptor-PSD-95 protein
interactions. Science 298:846–850
21. Nourry C, Grant SG, Borg J-P (2003) PDZ
domain proteins: plug and play! Sci STKE
2003:re7
22. Chi CN, Bach A, Strømgaard K, Gianni S,
Jemth P (2012) Ligand binding by PDZ
domains. Biofactors 38:338–348
23. Nevola L, Giralt E (2015) Modulating protein–protein interactions: the potential of peptides. Chem Commun (Camb) 51:3302–3315
24. Bach A, Clausen BH, Møller M, Vestergaard B,
Chi CN, Round A et al (2012) A high-affinity,
dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage. Proc Natl Acad Sci U S A
109:3317–3322
25. Sommer JB, Bach A, Mala ´ H, Strømgaard K,
Mogensen J, Pickering DS (2017) In vitro and
in vivo effects of a novel dimeric inhibitor of
PSD-95 on excitotoxicity and functional recovery after experimental traumatic brain injury.
Eur J Neurosci 45:238–248
26. Jensen J, Schousboe A, Pickering D (1998)
AMPA receptor mediated excitotoxicity in neocortical neurons is developmentally regulated
and dependent upon receptor desensitization.
Neurochem Int 32:505–513
PDZ Domain Peptide Inhibitors
177
AMP-mediated upregulation of the expression
of neuronal NO synthase in human A673 neuroepithelioma cells results in a decrease in the
level of bioactive NO production: analysis of
the signaling mechanisms that are involved.
Biochemistry 43:7197–7206
12. Schulz JB, Matthews RT, Klockgether T,
Dichgans J, Beal MF (1997) The role of mitochondrial dysfunction and neuronal nitric
oxide in animal models of neurodegenerative
diseases. Mol Cell Biochem 174:193–197
13. Pou S, Keaton L, Surichamorn W, Rosen GM
(1999) Mechanism of superoxide generation
by neuronal nitric-oxide synthase. J Biol
Chem 274:9573–9580
14. Grotta J, Clark W, Coull B, Pettigrew LC,
Mackay B, Goldstein LB, Meissner I,
Murphy D, LaRue L (1995) Safety and tolerability of the glutamate antagonist CGS 19755
(selfotel) in patients with acute ischemic stroke:
results of a phase IIa randomized trial. Stroke
26:602–605
15. Sveinbjornsdottir S, Sander J, Upton D,
Thompson P, Patsalos P, Hirt D, Emre M,
Lowe D, Duncan JS (1993) The excitatory
amino acid antagonist D-CPP-ene (SDZ
EAA-494) in patients with epilepsy. Epilepsy
Res 16:165–174
16. Albers G, Atkinson R, Kelley R, Rosenbaum D
(1995) Safety, tolerability, and pharmacokinetics of the N-methyl-D-aspartate antagonist
dextrorphan in patients with acute stroke.
Stroke 26:254–258
17. Albers GW, Goldstein LB, Hall D, Lesko LM,
Investigators AAS (2001) Aptiganel hydrochloride in acute ischemic stroke: a randomized
controlled trial. JAMA 286:2673–2682
18. Hoyte L, Barber P, Buchan A, Hill M (2004)
The rise and fall of NMDA antagonists for
ischemic stroke. Curr Mol Med 4:131–136
19. De Keyser J, Sulter G, Luiten PG (1999) Clinical trials with neuroprotective drugs in acute
ischaemic stroke: are we doing the right thing?
Trends Neurosci 22:535–540
20. Aarts M, Liu Y, Liu L, Besshoh S, Arundine M,
Gurd JW, Wang YT, Salter MW, Tymianski M
(2002) Treatment of ischemic brain damage by
perturbing NMDA receptor-PSD-95 protein
interactions. Science 298:846–850
21. Nourry C, Grant SG, Borg J-P (2003) PDZ
domain proteins: plug and play! Sci STKE
2003:re7
22. Chi CN, Bach A, Strømgaard K, Gianni S,
Jemth P (2012) Ligand binding by PDZ
domains. Biofactors 38:338–348
23. Nevola L, Giralt E (2015) Modulating protein–protein interactions: the potential of peptides. Chem Commun (Camb) 51:3302–3315
24. Bach A, Clausen BH, Møller M, Vestergaard B,
Chi CN, Round A et al (2012) A high-affinity,
dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage. Proc Natl Acad Sci U S A
109:3317–3322
25. Sommer JB, Bach A, Mala ´ H, Strømgaard K,
Mogensen J, Pickering DS (2017) In vitro and
in vivo effects of a novel dimeric inhibitor of
PSD-95 on excitotoxicity and functional recovery after experimental traumatic brain injury.
Eur J Neurosci 45:238–248
26. Jensen J, Schousboe A, Pickering D (1998)
AMPA receptor mediated excitotoxicity in neocortical neurons is developmentally regulated
and dependent upon receptor desensitization.
Neurochem Int 32:505–513
PDZ Domain Peptide Inhibitors
177