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Combined Transcriptomic and Proteomic Analyses of Cerebral Frontal Lobe Tissue Identified RNA Metabolism Dysregulation as One Potential Pathogenic Mechanism in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL).
Ritz, Marie-Françoise; Jenoe, Paul; Bonati, Leo; Engelter, Stefan; Lyrer, Philippe; Peters, Nils.
Afiliação
  • Ritz MF; Department of Biomedicine, Brain Tumor Biology Laboratory, University of Basel, and University Hospital of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
  • Jenoe P; Proteomics Core Facility, Biocenter, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
  • Bonati L; Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Petersgraben 4, 4031 Basel, Switzerland.
  • Engelter S; Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Petersgraben 4, 4031 Basel, Switzerland.
  • Lyrer P; Neurorehabilitation Unit, University of Basel and University Center for Medicine of Aging, Felix Platter Hospital, Burgfelderstrasse 101, 4055 Basel, Switzerland.
  • Peters N; Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Petersgraben 4, 4031 Basel, Switzerland.
Curr Neurovasc Res ; 16(5): 481-493, 2019.
Article em En | MEDLINE | ID: mdl-31657685
BACKGROUND: Cerebral small vessel disease (SVD) is an important cause of stroke and vascular cognitive impairment (VCI), leading to subcortical ischemic vascular dementia. As a hereditary form of SVD with early onset, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) represents a pure form of SVD and may thus serve as a model disease for SVD. To date, underlying molecular mechanisms linking vascular pathology and subsequent neuronal damage in SVD are incompletely understood. OBJECTIVE: We performed comparative transcriptional profiling microarray and proteomic analyses on post-mortem frontal lobe specimen from 2 CADASIL patients and 5 non neurologically diseased controls in order to identify dysregulated pathways potentially involved in the development of tissue damage in CADASIL. METHODS: Transcriptional microarray analysis of material extracted from frontal grey and white matter (WM) identified subsets of up- or down-regulated genes enriched into biological pathways mostly in WM areas. Proteomic analysis of these regions also highlighted cellular processes identified by dysregulated proteins. RESULTS: Discrepancies between proteomic and transcriptomic data were observed, but a number of pathways were commonly associated with genes and corresponding proteins, such as: "ribosome" identified by upregulated genes and proteins in frontal cortex or "spliceosome" associated with down-regulated genes and proteins in frontal WM. CONCLUSION: This latter finding suggests that defective expression of spliceosomal components may alter widespread splicing profile, potentially inducing expression abnormalities that could contribute to cerebral WM damage in CADASIL.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteoma / CADASIL / Transcriptoma / Substância Branca / Lobo Frontal Tipo de estudo: Prognostic_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Curr Neurovasc Res Assunto da revista: ANGIOLOGIA / NEUROLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteoma / CADASIL / Transcriptoma / Substância Branca / Lobo Frontal Tipo de estudo: Prognostic_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Curr Neurovasc Res Assunto da revista: ANGIOLOGIA / NEUROLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Suíça