Novel quaternary structures of the human prion protein globular domain.

Prion disease is caused by the misfolding of the cellular prion protein, PrPC, into a self-templating conformer, PrPSc. Nuclear magnetic resonance (NMR) and X-ray crystallography revealed the 3D structure of the globular domain of PrPC and the possibility of its dimerization via an interchain disulfide bridge that forms due to domain swap or by non-covalent association of two monomers. On the contrary, PrPSc is composed by a complex and heterogeneous ensemble of poorly defined conformations and quaternary arrangements that are related to different patterns of neurotoxicity. Targeting PrPC with molecules that stabilize the native conformation of its globular domain emerged as a promising approach to develop anti-prion therapies. One of the advantages of this approach is employing structure-based drug discovery methods to PrPC. Thus, it is essential to expand our structural knowledge about PrPC as much as possible to aid such drug discovery efforts. In this work, we report a crystallographic structure of the globular domain of human PrPC that shows a novel dimeric form and a novel oligomeric arrangement. We use molecular dynamics simulations to explore its structural dynamics and stability and discuss potential implications of these new quaternary structures to the conversion process.

Potenciales evocados de corta latencia: II tiempo de conducción central (TCC) / Short-latency evoked potentials: central conduction time (CCT)

Se describe la técnica para la obtención del tiempo de conducción central (TCC) en el análisis de los potenciales evocados somatosensoriales de corta latencia (PES-CL), determinándose los datos normativos de nuestro laboratorio en un grupo de 30 sujetos normales, compuestos por 17 mujeres y 13 hombres, con edades comprendidas entre 19 y 67 años. No se hallaron asimetrías izquierda-derecha ni para las latencias de P13, N20, ni para el TCC. Mientras para las latencias de P13 y N20, se encontraron diferencias significativas según la edad y el sexo, el TCC no dependía de estas variables. Se sugiere el empleo de un filtro de corte bajo de 0,5 Hz-5 para la derivación cefálica y uno de 100 Hz para la derivación cervical, definiéndose entonces el TCC como el intervalo interpico P13-N20