Monoclonal Antibodies as Novel Neurotherapeutic Agents in CNS Injury and Repair

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) believed to arise from a dysfunctional immune-mediated response in a genetically susceptible host. The actual cause of MS is not known, and there is ongoing debate about whether this CNS disorder is predominantly an inflammatory versus a degenerative condition. The afferent visual pathway (AVP) is frequently involved in MS, such that one in every five individuals affected presents with acute optic neuritis (ON). As a functionally eloquent system, the AVP is amenable to interrogation with highly reliable and reproducible tests that can be used to define a structural-functional paradigm of CNS injury. The AVP has numerous unique advantages as a clinical model of MS. In this review, the parameters and merits of the AVP model are highlighted. Moreover, the roles the AVP model may play in elucidating mechanisms of brain injury and repair in MS are described.

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Neurobiology of the CNS injury and repair: New roles of amino acids, growth factors and neuropeptides - Introduction

Amino Acids ◽

10.1007/s007260200032 ◽

2002 ◽

Vol 23 (1-3) ◽

pp. 217-219 ◽

Cited By ~ 6

Author(s):

H. S. Sharma

Keyword(s):

Amino Acids ◽

Growth Factors ◽

Cns Injury ◽

Injury And Repair

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A role for extracellular metallothioneins in CNS injury and repair

Neuroscience ◽

10.1016/j.neuroscience.2003.10.019 ◽

2004 ◽

Vol 123 (3) ◽

pp. 595-599 ◽

Cited By ~ 59

Author(s):

R.S Chung ◽

A.K West

Keyword(s):

Cns Injury ◽

Injury And Repair

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New therapeutic advances in CNS injury and repair

Expert Review of Neurotherapeutics ◽

10.1586/ern.12.87 ◽

2012 ◽

Vol 12 (8) ◽

pp. 901-905 ◽

Cited By ~ 4

Author(s):

Hari S Sharma ◽

Aruna Sharma

Keyword(s):

Cns Injury ◽

Injury And Repair

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Ultrastructural analysis of unique glycoconjugates in the rat olfactory system

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100124859 ◽

1992 ◽

Vol 50 (1) ◽

pp. 890-891

Author(s):

James E. Crandall ◽

Linda C. Hassinger ◽

Gerald A. Schwarting

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Monoclonal Antibodies ◽

Olfactory System ◽

Olfactory Bulbs ◽

Temporal And Spatial Patterns ◽

Carbohydrate Epitopes ◽

Olfactory Systems ◽

Temporal And Spatial ◽

Cell Surface Glycoconjugates

Cell surface glycoconjugates are considered to play important roles in cell-cell interactions in the developing central nervous system. We have previously described a group of monoclonal antibodies that recognize defined carbohydrate epitopes and reveal unique temporal and spatial patterns of immunoreactivity in the developing main and accessory olfactory systems in rats. Antibody CC2 reacts with complex α-galactosyl and α-fucosyl glycoproteins and glycolipids. Antibody CC1 reacts with terminal N-acetyl galactosamine residues of globoside-like glycolipids. Antibody 1B2 reacts with β-galactosyl glycolipids and glycoproteins. Our light microscopic data suggest that these antigens may be located on the surfaces of axons of the vomeronasal and olfactory nerves as well as on some of their target neurons in the main and accessory olfactory bulbs.

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Structural and Chemical Studies of Pathological Fibers in Human Neurofibrillary Degeneration

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010012031x ◽

1985 ◽

Vol 43 ◽

pp. 726-729

Author(s):

K.S. Kosik ◽

L.K. Duffy ◽

S. Bakalis ◽

C. Abraham ◽

D.J. Selkoe

Keyword(s):

Monoclonal Antibodies ◽

Alzheimer Disease ◽

Human Brain ◽

Neurofibrillary Tangles ◽

Morphological Analysis ◽

High Specificity ◽

Cytoskeletal Proteins ◽

Neuritic Plaque ◽

Protein Chemistry ◽

Chemical Studies

The major structural lesions of the human brain during aging and in Alzheimer disease (AD) are the neurofibrillary tangles (NFT) and the senile (neuritic) plaque. Although these fibrous alterations have been recognized by light microscopists for almost a century, detailed biochemical and morphological analysis of the lesions has been undertaken only recently. Because the intraneuronal deposits in the NFT and the plaque neurites and the extraneuronal amyloid cores of the plaques have a filamentous ultrastructure, the neuronal cytoskeleton has played a prominent role in most pathogenetic hypotheses.The approach of our laboratory toward elucidating the origin of plaques and tangles in AD has been two-fold: the use of analytical protein chemistry to purify and then characterize the pathological fibers comprising the tangles and plaques, and the use of certain monoclonal antibodies to neuronal cytoskeletal proteins that, despite high specificity, cross-react with NFT and thus implicate epitopes of these proteins as constituents of the tangles.

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