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' This study compared idebenone to oxiracetam. b Alzheimer's Disease Assessment Scale, cognitive portion c Alzheimer's Disease Assessment Scale, total score. d Clinical Global Impression Scale. e This study compared idebenone to nebracetam. ' This study compared idebenone to oxiracetam. b Alzheimer's Disease Assessment Scale, cognitive portion c Alzheimer's Disease Assessment Scale, total score. d Clinical Global Impression Scale. e This study compared idebenone to nebracetam. and found...

Model Of Parkinsonism

Metallothionein (MT) isoforms are low molecular weight (6000-7000) zinc-binding proteins containing 60-61 amino acid residues, 25-30 cysteine, no aromatic amino acids or disulfide bonds, and binding 5-7 g zinc mole of protein (89,90). The mammalian MT family consists of four similar but distinct isoforms, designated as MT I-IV. MT I and MT II isoforms were first identified in the rat brain in our laboratory by Itoh et al. (91). MT III containing 68 amino acids, also known as a growth inhibitory...

References

Lang, A.E. and Lozano, A.M. (1998) Parkinson's disease. N. Engl. J. Med. 339, 1044-1053. 2. Jenner, P. (1998) Oxidative mechanisms in nigral cell death in Parkinson's disease. Mov. Disord. 13(suppl 1), 24-34. 3. Polymeropoulos, M.H., Higgings, J.H., Golbe, L.I., et al. (1996) Mapping of a gene for Parkinson's disease to chromosome 4q21-q23. Science 274, 1197-1199. 4. Polymeropoulos, M.H., Lavedan, C., Leroy, E., et al. (1997) Mutation in the a-synuclein gene identified in families with...

Pain Sensitization and Hyperalgesia

It is now well established that modifications in nociceptor function as well as altered processing of nociceptive information in the spinal cord contribute to long-term changes in nociception ultimately leading to hyperalgesia and allodynia (161). Pain is the perception of an aversive or unpleasant sensation originating from a given region of the body and thus involves integration and elaboration of the nociceptive input. Therefore, the nature of pain is highly subjective and this makes it...

Neuromelanin

Neuromelanin is a black pigment found in certain monoaminergic neuron subpopulations of some animal species, including primates (18). This insoluble pigment results from the autooxidation, condensation, and polymerization of DA and its oxidation products (8). Although some neuromelanin accumulates in DA cell bodies during the normal aging process, those SNpc DA neurons that contain the greatest amounts of neuromelanin die preferentially in PD compared to those with less neuromelanin (19)....

Gsh

Figure 3 Illustration of ROS-scavenging enzymes. concomitant weakening of ROS protective mechanisms. The main ROS scavengers are superoxide dismutase (SOD), catalase, and glutathione peroxidase (Fig. 3), as well as several small molecules with strong antioxidant properties, such as glutathione, vitamin C, vitamin E, and ubiquinone. Among the ROS-scavenging enzymes in PD, SOD has received the lion's share of investigation. One finding that makes SOD, and more particularly the cytosolic form of...

Free Radicals Derived From Catecholamines

Catecholamines are themselves potent antioxidants but they are easily oxidized to highly neurotoxic o-quinones (Fig. 2). Vulpian (95) noted in 1856 that adrenal gland tissue exposed to air turns red. This red pigment was later identified as adrenochrome, but it was thought for many years that this pathway of catechola-mine metabolism never occurred in vivo. Recently, however, conclusive evidence has been obtained that this pathway does indeed occur in the body, particularly in the brain where...

Role Of Free Radicals In Brain Disease A Schizophrenia

There are several reports that spine numbers, and thus synapses, in the cortex and striatum in schizophrenic brain are reduced by 50 (28-30,70). There are also reports that certain brain areas have loss of neuropil (30,82,93). It is not clear, however, if this is because they were never formed properly or were pruned excessively. It is possible that this finding represents an imbalance in the dynamic process that controls the formation and deletion of synapses. I have put forward the hypothesis...

Biochemistry Nitric Oxide Synthase

Since the first reports on mammalian NO synthesis (9,10) knowledge about NO biosynthesis has increased rapidly. In all tissue studied so far, NO is generated by nitric oxide synthase (NOS), together with l-citrulline, from one of the guanidino nitrogens of the amino acid l-arginine, in the presence of molecular oxygen (Fig. 1). There is actually a family of NO synthases that constitute a rather complex Figure 1 Mechanism of production of NO at synapses. NO is generated from L-arginine by nNOS....

Free Radicals and Antioxidants in Neurological Disorders

ROS and Parkinson's Disease A View to a Kill Serge Przedborski and Vernice R. Jackson-Lewis 14. Nitric Oxide Overproduction and Oxidative Stress in Human Idiopathic Parkinson's Disease 291 Emilia Mabel Gatto, Natalia Andrea Riobo, Maria Cecilia Carreras, and Juan Jose Poderoso 15. Molecular and Cellular Aspects of Oxidative Damage in Alzheimer's Disease 313 Mark A. Smith and George Perry 16. Free Radical-Mediated Disruption of Cellular Ion Homeostasis, Mitochondrial Dysfunction, and...