Getting to NO Alzheimer’s Disease: Neuroprotection versus Neurotoxicity Mediated by Nitric Oxide

Table 1

Alterations in the expression and activity of nitric oxide synthase (NOS) enzymes in Alzheimer’s disease (AD) tissue and animal models.

Author	Methods	Tissue type/control	Results
Hyman et al., 1992 [65]	Immunocytochemistry staining of NOS in neurons using rabbit polyclonal antibody and peroxidase linked secondary antibody.	Hippocampus and temporal neocortex from AD and control postmortem brains.; AD mean age: 80.85 ± 2.0 years.; Control mean age: 60.4 ± 5.9 years.; Five control subjects had brain abnormalities upon postmortem examination.	No significant difference between the expressions of NOS in AD neurons in comparison to controls.
Dorheim et al., 1994 [66]	L-Citrulline (coproduct of NO) was used as a marker of NOS activity in microvessels.	Brain microvessels from AD and control patients.	Significant increase in NOS activity in AD brain microvessels.
Benzing and Mufson, 1995 [67]	Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) used as a marker for NOS in neurons.	AD and control postmortem brains (age, sex, brain weight, and postmortem interval matched).	Significantly higher levels of NADPH expression in AD neurons in comparison to controls.
Norris et al., 1996 [68]	mRNA expression levels of nNOS and NADPH-d staining used as markers for nNOS expression.	Frontal cortex, visual cortex, and hippocampus of AD and control postmortem brains.	A decrease (not significant) in cellular abundance of nNOS in AD brains in comparison to controls. A significant decrease in the number of cells expressing nNOS in distinct brain regions.
Gargiulo et al., 2000 [69]	Immunohistochemistry staining with monoclonal antibodies for NOS and protein kinase C (PKC) expression.	Regions of the temporalis gyrus from AD and control postmortem brains.	A significant decrease in NOS levels from AD brains, no change in PKC expression levels.
Lüth et al., 2001 [70]	Immunohistochemistry and western blotting of iNOS and eNOS expression levels in three tissue types.	Sporadic AD postmortem brains, human APP transgenic mice, and electrolytic cortical lesions in rat tissue. Age and postmortem interval matched for human controls. Aged and nontransgenic mice matched controls.	Increased expression of iNOS and eNOS in both human AD and transgenic mice reactive astrocytes in comparison to controls.
Venturini et al., 2002 [71]	Optical, fluorescence, and NMR spectroscopy was used to determine interaction with NADPH-d and downstream effects on NOS activity.	Neuronal and glioma-like rat cell lines and appropriate controls.	interacts with NADPH-d, decreasing the availability of the substrate for cNOS and strongly reducing cNOS activity.
Stepanichev et al., 2008 [72]	NADPH-d histo- and immunocytochemistry used as a marker for nNOS and iNOS expression.	Cerebral and hippocampus administered rat tissue and non-Aβ rat tissue as controls.	did not influence nNOS or iNOS mRNA or protein expression. increased nNOS activity but not iNOS.