Chaperoning brain diseases (original) (raw)
- News & Views
- Published: 05 March 1998
Neurodegeneration
Nature volume 392, pages 23–24 (1998)Cite this article
- 341 Accesses
- 74 Citations
- Metrics details
A common feature of several neurodegenerative disorders — including Alzheimer's and Parkinson's diseases — is a pathogenetic mechanism which is similar to that proposed for prion diseases (Table 1). The proteins involved have poorly structured native conformations that can be destabilized further by genetic mutations, leading them to adopt β-sheet structures. These, in turn, result in the formation of insoluble, disease-causing protein aggregates in the brain. Under some conditions the aggregates can then act as a seed, inducing the normal protein to adopt the abnormal conformation1,2. But might these apparent ‘errors in protein folding’ be mediated by other macromolecules? This obvious but unresolved issue is addressed by two papers3,4 from Lindquist and colleagues in Proceedings of the National Academy of Sciences.
Table 1 ‘Aggregate-forming’ neurodegenerative diseases
The idea that a molecular chaperone might participate in the conversion process seems plausible and has, in fact, been suggested for the prion-related disorders. Here, the apparent ‘species barrier’ (where one species of animal is resistant to infection by prions derived from another species) has led to the conclusion that another component must feature in the conversion of the normal prion protein, PrPC, into its infectious and pathological form, PrPres. Indeed, Prusiner and colleagues2 have proposed that the conversion of PrPC to PrPres is facilitated by a host component, referred to as protein X.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Additional access options:
Figure 1: Relationships between protein folding, neurodegenerative diseases and ageing.
References
- Ghiso, J., Wisniewski, T. & Frangione, B. Mol. Neurobiol. 8, 49–64 (1994).
Google Scholar - Paulson, H. L.et al. Neuron 19, 333–334 (1997).
Google Scholar - Schirmer, E. C. & Lindquist, S. Proc. Natl Acad. Sci. USA 94, 13932–13937 (1997).
Google Scholar - DebBurman, S. K.et al. Proc. Natl Acad. Sci. USA 94, 13938–13943 (1997).
Google Scholar - Wisniewski, T., Ghiso, J. & Frangione, B. Neurobiol. Dis. 4, 313–328 (1997).
Google Scholar - Tatzelt, J.et al. Proc. Natl Acad. Sci. USA 92, 2944–2948 (1995).
Google Scholar - Liu, Y. C.et al. J. Biol. Chem. 264, 12037–12043 (1989).
Google Scholar - Fargnoli, J. Proc. Natl Acad. Sci. USA 87, 846–850 (1990).
Google Scholar - Orgel, L. E. Proc. Natl Acad. Sci. USA 49, 517–521 (1963).
Google Scholar - Prusiner, S. B. Science 278, 245–251 (1997).
Google Scholar - Frangione, B., Wisniewski, T., Castanol, E. M. & Ghiso, J. in Research in Alzheimer's Disease and Related Disorders (eds Iqbal, K., Mortimer, J. A., Winblad, B. & Wisniewski, H. M.) 563-568 (Wiley, New York, 1995).
- Polymeropoulos, M. H.et al. Science 276, 2045–2047 (1997).
Google Scholar - Goedert, M. Nature 388, 232–234 (1997).
Article ADS CAS Google Scholar - Nussbaum, R. L. & Polymeropoulos M. H. Hum. Mol. Genet. 6, 1687–1691 (1997).
Google Scholar - Heinz, N. & Zoghbi, H. Nature Genet. 16, 325–327 (1997).
Article Google Scholar - Ross, C. A. Neuron 19, 1147–1150 (1997).
Google Scholar
Author information
Authors and Affiliations
- the Department of Surgery, Medicine and Physiology, University of California at San Francisco, San Francisco, 94143, California, USA
William J. Welch - the Division of Neuropathology, Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, 44106, Ohio, USA
Pierluigi Gambetti
Authors
- William J. Welch
You can also search for this author inPubMed Google Scholar - Pierluigi Gambetti
You can also search for this author inPubMed Google Scholar
Rights and permissions
About this article
Cite this article
Welch, W., Gambetti, P. Chaperoning brain diseases.Nature 392, 23–24 (1998). https://doi.org/10.1038/32049
- Issue Date: 05 March 1998
- DOI: https://doi.org/10.1038/32049