2 documents found, page 1 of 1
A conformational switch controlling the toxicity of the prion protein
Frontzek, K; Bardelli, M; Senatore, A; Henzi, A; Reimann, RR; Bedir, S; Marino, M; Hussain, R; Jurt, S; Meisl, G; Pedotti, M; Mazzola, F; Siligardi, GPrion infections cause conformational changes of the cellular prion protein (PrPC) and lead to progressive neurological impairment. Here we show that toxic, prion-mimetic ligands induce an intramolecular R208-H140 hydrogen bond (‘H-latch’), altering the flexibility of the α2–α3 and β2–α2 loops of PrPC. Expression of a PrP2Cys mutant mimicking the H-latch was constitutively toxic, whereas a PrPR207A mutant unabl...
PHACTR1 genetic variability is not critical in small vessel ischemic disease pa...
Messerschmidt, C; Foddis, M; Blumenau, S; Müller, S; Bentele, K; Holtgrewe, M; Kun-Rodrigues, C; Alonso, I; Carmo Macario, M; Morgadinho, AS; Velon, AGRecently, several genome-wide association studies identified PHACTR1 as key locus for five diverse vascular disorders: coronary artery disease, migraine, fibromuscular dysplasia, cervical artery dissection and hypertension. Although these represent significant risk factors or comorbidities for ischemic stroke, PHACTR1 role in brain small vessel ischemic disease and ischemic stroke most important survival mechan...