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Prion diseases of mammals: epidemiology, genetics, and pathogenesis

Le malattie prioniche dei mammiferi: epidemiologia, genetica, e patogenesi

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Abstract

Neuronal vacuolation (spongiosis), neuronal death, and a severe glial reaction are the histological hallmarks of transmissible spongiform encephalopathies (TSEs), also known as prion diseases. A rich collection of biophysical, biochemical, and immunological experiments indicates that the causative agent of TSEs, which was named prion, does not contain nucleic acids that would encode its own proteins, as is the case for all other known pathogens. Besides, prion infections do not appear to elicit adaptive immune responses. A defining characteristics of TSEs is, instead, the deposition — mainly in the central nervous and lymphoreticular systems — of an aggregated, structurally anomalous protein (denoted PrPSc), which was found to represent a conformational variant of the cellular prion protein PrPC. Biophysical and biochemical evidence connects PrPSc and PrPC. Although TSEs are generally transmissible, mounting evidence suggests that prions may be involved also in a number of non-transmissible neurodegenerative pathologies.

Riassunto

La vacuolizzazione neuronale (spongiosi), la morte neuronale, e una pronunciata reazione gliale sono i connotati istologici delle encefalopatie spongiformi trasmissibili (TSE), alternativamente denominate malattie prioniche. Una ricca collezione di prove biofisiche, biochimiche, e immunologiche indica che l’agente eziopatologico delle TSE, denominato prione, non contiene acidi nucleici specifici a se stesso codificanti i propri costituenti proteici, come invece è il caso per tutti gli altri agenti patogeni conosciuti. Inoltre, l’infezione prionica non sembra indurre risposte immunitarie adattive. Una caratteristica definente le TSE è invece la deposizione — prevalentemente nel sistema nervoso centrale e in quello linforeticolare — di una proteina aggregata e strutturalmente anomala (denominata PrPSc) che risulta essere una variante conformazionale di una proteina corporea normale, cioè la PrPC codificata dal genePrnp. Prove biochimiche e genetiche connettono le TSE con la PrPSc e il genePrnp. Nonostante le TSE siano per definizione trasmissibili, viene oggi riconosciuto un crescente numero di patologie neurodegenerative non necessariamente infettive.

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  1. Institute of Neuropathology, University Hospital of Zürich, Schmelzbergstrasse, 12, 8091, Zürich, Svizzera

    Adriano Aguzzi

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Tenuta nella seduta del 23 maggio 2005, in occasione della Giornata Lincea in onore di Camillo Golgi sul tema «Problemi attuali e prospettive future nello studio delle malattie neurodegenerative».

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Aguzzi, A. Prion diseases of mammals: epidemiology, genetics, and pathogenesis. Rend. Fis. Acc. Lincei 17, 355–376 (2006). https://doi.org/10.1007/BF02904771

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