Nitric Oxide as an Initiator of Brain Lesions During the Development of Alzheimer Disease

Abstract

Nitric oxide (NO) is an important regulatory molecule for the host defense that plays a fundamental role in the cardiovascular, immune, and nervous systems. NO is synthesized through the conversion of L-arginine to L-citrulline by the enzyme NO synthase (NOS), which is found in three isoforms classified as neuronal (nNOS), inducible (iNOS), and endothelial (eNOS). Recent evidence supports the theory that this bioactive molecule has an influential role in the disruption of normal brain and vascular homeostasis, a condition known to elucidate chronic hypoperfusion which ultimately causes the development of brain lesions and the pathology that typify Alzheimer disease (AD). In addition, vascular NO activity appears to be a major contributor to this pathology before any overexpression of NOS isoforms is observed in the neuron, glia, and microglia of the brain tree, where the overexpression the NOS isoforms causes the formation of a large amount of NO. We hypothesize that since an imbalance between the NOS isoforms and endothelin-1 (ET-1), a human gene that encodes for blood vessel constriction, can cause antioxidant system insufficiency; by using pharmacological intervention with NO donors and/or NO suppressors, the brain lesions and the downstream progression of brain pathology and dementia in AD should be delayed or minimized.

Reversing Synapse Loss in Alzheimer's Disease: Rho-Guanosine Triphosphatases and Insights from Other Brain Disorders

“…The functional consequences of this decrease are not clear, but, interestingly, kalirin-7 associates with inducible nitric oxide synthase (iNOS) in the hippocampus resulting in the downregulation of its enzymatic activity [76,78]. These data are in line with the findings that iNOS levels and activity are increased in AD [79,80], suggesting that the decrease of kalirin-7 in patients with AD contributes to further augment iNOS activity and exacerbate AD pathology [76]. Kalirin-7 decrease may also have a critical causative role in dendritic spine pathology in AD.…”

Phytochemical analysis, antioxidant and antilipid peroxidation effects of a medicinal plant, Adhatoda vasica

“…It transmits signals from vascular endothelial cells to vascular smooth muscle cells, resulting in vasodilatation (Aliev et al 2009). It plays an important role in vital physiological functions in the respiratory, immune, neuromuscular and other systems.…”

“…It plays an important role in vital physiological functions in the respiratory, immune, neuromuscular and other systems. This molecule also regulates the release of neurotransmitters, and is involved in neuronal excitability, learning and memory processes, as well as inflammatory bowel syndrome, sepsis, septic shock, cephalalgia, dementia, multiple sclerosis and stroke (Aliev et al 2009). In addition, it has been shown that nitric oxide modulates neurotoxin-induced cellular damage and is involved in neuronal cell death in Parkinson's disease and other neurodegenerative disorders such as Alzheimer's disease (Aliev et al 2009).…”

“…This molecule also regulates the release of neurotransmitters, and is involved in neuronal excitability, learning and memory processes, as well as inflammatory bowel syndrome, sepsis, septic shock, cephalalgia, dementia, multiple sclerosis and stroke (Aliev et al 2009). In addition, it has been shown that nitric oxide modulates neurotoxin-induced cellular damage and is involved in neuronal cell death in Parkinson's disease and other neurodegenerative disorders such as Alzheimer's disease (Aliev et al 2009). A number of related reports suggest that nitric oxide may modulate iron-catalysed oxidation reactions such as the superoxide-anion driven Fenton's reaction, resulting in the production of strong oxidants such as the hydroxyl radical and organometallic complexes (Dadashpour et al 2011).…”

Antioxidant, Anti-Lipid Peroxidative and Antimicrobial Properties of the Epiphytic Fern, Pyrrosia Heterophylla (L.) M. G. Price

“…Earlier works have suggested that DPPH scavenging is achieved by an antioxidant by a hydrogen atom transfer process (HAT) [21]. The antioxidant phytochemicals in the extracts work possibly through the donation of hydrogen to form a stable DPPH molecule [22]. Phenolic compounds like gallic acid and flavonoids like epicatechin are shown to exert their antioxidant activity through hydrogen donating mechanism [23].…”