Nitric oxide synthases: targets for therapeutic strategies in neurological diseases

• Published in: Cellular and molecular life sciences : CMLS Vol. 55; no. 8-9; pp. 1029 - 1035
• Main Authors: Chabrier, P E, Demerlé-Pallardy, C, Auguet, M
• Format: Journal Article
• Language: English
• Published: Switzerland Springer Nature B.V 01.07.1999; Birkhäuser Verlag
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - enzymology; Alzheimer's disease; Amidines - pharmacology; Amidines - therapeutic use; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - drug therapy; Amyotrophic Lateral Sclerosis - enzymology; Animals; Antioxidants; Benzylamines - pharmacology; Benzylamines - therapeutic use; Brain Injuries - drug therapy; Brain Ischemia - drug therapy; Enzyme Induction; Enzymes; Excitotoxicity; Glutamic acid; Humans; Huntington Disease - drug therapy; Huntington Disease - enzymology; Huntington's disease; Inhibitors; Ischemia; Mice; Mice, Neurologic Mutants; Mice, Transgenic; Mitochondria; Movement disorders; Nerve Degeneration - drug therapy; Nerve Degeneration - metabolism; Nerve Degeneration - prevention & control; Nerve Tissue Proteins - antagonists & inhibitors; Nervous System Diseases - drug therapy; Neurodegenerative diseases; Neurological diseases; Neurological disorders; Neuroprotection; Neurotransmitters; Nitric oxide; Nitric Oxide - adverse effects; Nitric Oxide - physiology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase Type I; Nitric-oxide synthase; Organ Specificity; Oxidative stress; Parkinson's disease; Peroxynitrite; Polymethacrylic Acids - pharmacology; Pyrazines - pharmacology; Pyrazines - therapeutic use; superoxide anions; Thiophenes - pharmacology; Thiophenes - therapeutic use; Traumatic brain injury
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s000180050353

Glutamate excitotoxicity, oxidative stress, and mitochondrial dysfunctions are common features leading to neuronal death in cerebral ischemia, traumatic brain injury, Parkinson's disease, Huntington's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Nitric oxide (NO) alone or in cooperation with superoxide anion and peroxynitrite is emerging as a predominant effector of neurodegeneration The use of NO synthase (NOS) inhibitors and mutant mice lacking each NOS isoform have provided evidence for the injurious effects of NO derived from neuronal or inducible isoforms. New neuroprotective strategies have been proposed with selective NOS inhibitors for the neuronal (ARL17477) or the inducible (1400 W) isoforms or with compounds combining in one molecule selective nNOS inhibition and antioxidant properties (BN 80933), in experimental ischemia-induced acute neuronal damage. The efficacy of these new strategies is well established in acute neuronal injury but remains to be determined in more chronic neurological diseases.