Prion proteins as memory molecules: an hypothesis.
Prions are infectious agents widely implicated in a variety of mammalian neurodegenerative diseases generally referred to as transmissible spongiform encephalopathies. Their infectivity is primarily associated with an aberrant conformation of a host-encoded protein, the prion protein, induced by the prion itself in an autocatalytic reaction. The physiological function of this protein is not known. In this paper we suggest that alternative conformations of the prion protein, other than its pathological scrapie state, exist and that the self-sustaining autocatalytic propagation of these states underlies its normal cellular function. In kinetic model calculations we show that the prion protein may constitute a bi-stable molecular switch that can structurally encode and stably store information. A number of cases of prion involvement in normal cellular function and ample molecular detail of pathological prion propagation are cited and correlated to substantiate the implications of this tenet. Our contention is that the prion hypothesis should be extended to a wide variety of physiological processes. We propose that prion proteins are stable determinants of phenotype, operating in diverse functions possibly including memory.
Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest, Hungary.
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Tompa
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Friedrich
D000818:Animals; D006801:Humans; D008568:Memory / Q000502:physiology*; D008959:Models, Neurological; D011328:Prions / Q000502:physiology*
D011328:Prions