Chaperoning brain diseases (original) (raw)

Neurodegeneration

Nature volume 392, pages 23–24 (1998)Cite this article

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

Full size table

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.

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Figure 1: Relationships between protein folding, neurodegenerative diseases and ageing.

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Authors and Affiliations

  1. the Department of Surgery, Medicine and Physiology, University of California at San Francisco, San Francisco, 94143, California, USA
    William J. Welch
  2. the Division of Neuropathology, Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, 44106, Ohio, USA
    Pierluigi Gambetti

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  1. William J. Welch
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  2. Pierluigi Gambetti
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Welch, W., Gambetti, P. Chaperoning brain diseases.Nature 392, 23–24 (1998). https://doi.org/10.1038/32049

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