Gerstmann-Straüssler-Scheinker PRNP P102L-129V mutation

Walter de Gruyter GmbH - Tập 2 Số 1 - 2011
Isidro Ferrer1, Margarita Carmona1, Rosa Blanco1, María Jesús Rey Recio2, R. M. San Segundo3
1Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL Hospital Universitari de Bellvitge, Universitat de Barcelona, CIBERNED, Hospitalet de LLobregat, Barcelona, Spain
2Banc de Teixits Neurologics, Hospital Clinic-Universitat de Barcelona, Barcelona, Spain
3Centre Sociosanitari LLevant, Tarragona, Spain

Tóm tắt

Abstract

Neuropathological and biochemical studies in a case of Gerstmann-Straüssler-Scheinker disease bearing the PRNP P102L-129V mutation showed numerous multicentric PrPres in the cerebral cortex, striatum, thalamus and cerebellum, PrPres globular deposits in the anterior and posterior horns of the spinal cord, and multiple granular PrPres deposits in the grey and white matter of the encephalon and spinal cord. Western blots with antiPrPres antibodies revealed several weak bands ranging from 36 to 66 kDa, weak bands of 29 and 24 kDa, a strong band of about 20 kDa, a low band of molecular weight around 15 kDa and a weaker band of about 7 kDa. Spongiform degeneration was absent. Hyper-phosphorylated 3R and 4R tau occurred in dystrophic neurites surrounding PrPres plaques, neuropil threads and, to a lesser degree, in the form of neurofibrillary tangles. Gel electrophoresis of sarkosyl-insoluble fractions and western blotting with anti-phospho-tau antibodies showed a pattern similar to that seen in Alzheimer disease cases run in parallel. Dystrophic neurites in the vicinity of PrPres plaques were enriched in voltage dependent anion channel thus suggesting abnormal accumulation of mitochondria. These changes were associated with increased oxidative damage in neurons and astrocytes, Finally, increased expression of active stress kinases, that have the capacity to phosphorylate tau in vitro, p38 (p-38-P) and SAPK/ JNK (SAPK/JNK-P) was found in cell processes surrounding PrP plaques. Together, these observations provide evidences of mitochondrial abnormalities, and increased oxidative stress damage and oxidative stress responses in GSS bearing the PRNP P102L-129V mutation.

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