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Science 14 June 2002:
Vol. 296. no. 5575, pp. 1991 - 1995
DOI: 10.1126/science.1067122
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Review

Toxic Proteins in Neurodegenerative Disease

J. Paul Taylor,1* John Hardy,2 Kenneth H. Fischbeck1

A broad range of neurodegenerative disorders is characterized by neuronal damage that may be caused by toxic, aggregation-prone proteins. As genes are identified for these disorders and cell culture and animal models are developed, it has become clear that a major effect of mutations in these genes is the abnormal processing and accumulation of misfolded protein in neuronal inclusions and plaques. Increased understanding of the cellular mechanisms for disposal of abnormal proteins and of the effects of toxic protein accumulation on neuronal survival may allow the development of rational, effective treatment for these disorders.

1 Neurogenetics Branch, National Institute of Neurological Disorders and Stroke,
2 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
*   To whom correspondence should be addressed. E-mail: taylorjp{at}ninds.nih.gov

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Molecular Distinction between Pathogenic and Infectious Properties of the Prion Protein.
R. Chiesa, P. Piccardo, E. Quaglio, B. Drisaldi, S. L. Si-Hoe, M. Takao, B. Ghetti, and D. A. Harris (2003)
J. Virol. 77, 7611-7622
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Specific Compositions of Amyloid-{beta} Peptides as the Determinant of Toxic {beta}-Aggregation.
Y. Yoshiike, D.-H. Chui, T. Akagi, N. Tanaka, and A. Takashima (2003)
J. Biol. Chem. 278, 23648-23655
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A cell-based assay for aggregation inhibitors as therapeutics of polyglutamine-repeat disease and validation in Drosophila.
B. L. Apostol, A. Kazantsev, S. Raffioni, K. Illes, J. Pallos, L. Bodai, N. Slepko, J. E. Bear, F. B. Gertler, S. Hersch, et al. (2003)
PNAS 100, 5950-5955
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The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndrome.
R. Willemsen, M. Hoogeveen-Westerveld, S. Reis, J. Holstege, L.-A. W.F.M. Severijnen, I. M. Nieuwenhuizen, M. Schrier, L. van Unen, F. Tassone, A. T. Hoogeveen, et al. (2003)
Hum. Mol. Genet. 12, 949-959
   Abstract »    Full Text »    PDF »
Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein.
J. P. Taylor, F. Tanaka, J. Robitschek, C. M. Sandoval, A. Taye, S. Markovic-Plese, and K. H. Fischbeck (2003)
Hum. Mol. Genet. 12, 749-757
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Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: A magnetic resonance microscopy and stereologic analysis.
J. M. Redwine, B. Kosofsky, R. E. Jacobs, D. Games, J. F. Reilly, J. H. Morrison, W. G. Young, and F. E. Bloom (2003)
PNAS 100, 1381-1386
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Suppression of polyglutamine-induced protein aggregation in Caenorhabditis elegans by torsin proteins.
G. A. Caldwell, S. Cao, E. G. Sexton, C. C. Gelwix, J. P. Bevel, and K. A. Caldwell (2003)
Hum. Mol. Genet. 12, 307-319
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Folding and Function of the Troponin Tail Domain. EFFECTS OF CARDIOMYOPATHIC TROPONIN T MUTATIONS.
A. Hinkle and L. S. Tobacman (2003)
J. Biol. Chem. 278, 506-513
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