[Frontiers in Bioscience 9, 763-776, January 1, 2004]

NITRIC OXIDE NEUROTOXICITY IN NEURODEGENERATIVE DISEASES

Kathleen M.K. Boje

Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Nitric Oxide Biochemistry
3.1. Nitric Oxide Synthase Isoforms
3.2. Synthesis and Metabolism of Nitric Oxide
4. Neuroprotective / Neurotoxic Mechanisms Of Nitric Oxide And Reactive Nitrogen Oxide Species
4.1. Mechanisms Of Neuroprotection
4.2. Mechanisms Of Toxicity
4.2.1. Molecular Mechanisms
4.2.2. Cell Biological Mechanisms
4.2.3. Excitotoxicity
4.2.4. Neuroinflammation
4.2.5. Blood-Brain Barrier and Blood-Cerebrospinal Fluid Barrier Toxicity
5. Nitric Oxide In Neurodegenerative Diseases
5.1. Acquired Immune Deficiency Syndrome (AIDS) Dementia Complex
5.2. Amyotrophic Lateral Sclerosis
5.3. Alzheimer's Disease
5.4. Huntington's Disease
5.5. Multiple Sclerosis
5.6. Parkinson's Disease
6. Perspective
7. References

1. ABSTRACT

Nitric oxide (nitrogen monoxide; NO) is a simple molecule with diverse biological functions. NO and related reactive nitrogen oxide species (RNOS) mediate intricate physiological and pathophysiological effects in the central nervous system. Depending on environmental conditions, NO and RNOS can initiate and mediate neuroprotection or neurotoxicity either exclusively or synergistically with other effectors. The focus of this review is limited to the neuroprotectant / neurotoxic role of NO in Acquired Immune Deficiency Syndrome (AIDS) Dementia Complex (aka HIV - Associated Dementia; HAD) Amyotrophic Lateral Sclerosis (aka Lou Gehrig's Disease), Alzheimer's Disease, Huntington's Disease, Multiple Sclerosis and Parkinson's Disease. This review will shed light on the question: "How important is NO in neurodegenerative diseases?"