Abstract
Functional genomics applied to the study of RNA expression profiles identified several abnormal molecular processes in experimental prion disease. However, only a few similar studies have been carried out to date in a naturally occurring human prion disease. To better characterize the transcriptional cascades associated with sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, we investigated the global gene expression profile in samples from the frontal cortex of 10 patients with sCJD and 10 non-neurological controls by microarray analysis. The comparison identified 333 highly differentially expressed genes (hDEGs) in sCJD. Functional enrichment Gene Ontology analysis revealed that hDEGs were mainly associated with synaptic transmission, including GABA (q value = 0.049) and glutamate (q value = 0.005) signaling, and the immune/inflammatory response. Furthermore, the analysis of cellular components performed on hDEGs showed a compromised regulation of vesicle-mediated transport with mainly up-regulated genes related to the endosome (q value = 0.01), lysosome (q value = 0.04), and extracellular exosome (q value < 0.01). A targeted analysis of the retromer core component VPS35 (vacuolar protein sorting-associated protein 35) showed a down-regulation of gene expression (p value= 0.006) and reduced brain protein levels (p value= 0.002). Taken together, these results confirm and expand previous microarray expression profile data in sCJD. Most significantly, they also demonstrate the involvement of the endosomal-lysosomal system. Since the latter is a common pathogenic pathway linking together diseases, such as Alzheimer’s and Parkinson’s, it might be the focus of future studies aimed to identify new therapeutic targets in neurodegenerative diseases.
| Original language | English |
|---|---|
| Journal | Molecular Neurobiology |
| DOIs | |
| Publication status | E-pub ahead of print - 2018 |
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Keywords
- Genome-wide expression
- Human prion
- Membrane trafficking
- Retromer
- Sporadic Creutzfeldt-Jakob disease
- VPS35
ASJC Scopus subject areas
- Neuroscience (miscellaneous)
- Neurology
- Cellular and Molecular Neuroscience
Cite this
Analysis of RNA Expression Profiles Identifies Dysregulated Vesicle Trafficking Pathways in Creutzfeldt-Jakob Disease. / Bartoletti-Stella, Anna; Corrado, Patrizia; Mometto, Nicola; Baiardi, Simone; Durrenberger, Pascal F.; Arzberger, Thomas; Reynolds, Richard; Kretzschmar, Hans; Capellari, Sabina; Parchi, Piero.
In: Molecular Neurobiology, 2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Analysis of RNA Expression Profiles Identifies Dysregulated Vesicle Trafficking Pathways in Creutzfeldt-Jakob Disease
AU - Bartoletti-Stella, Anna
AU - Corrado, Patrizia
AU - Mometto, Nicola
AU - Baiardi, Simone
AU - Durrenberger, Pascal F.
AU - Arzberger, Thomas
AU - Reynolds, Richard
AU - Kretzschmar, Hans
AU - Capellari, Sabina
AU - Parchi, Piero
N1 - Ricercatori distaccati presso IRCCS a seguito Convenzione esclusiva con Università di Bologna (Capellari Sabina, Parchi Piero).
PY - 2018
Y1 - 2018
N2 - Functional genomics applied to the study of RNA expression profiles identified several abnormal molecular processes in experimental prion disease. However, only a few similar studies have been carried out to date in a naturally occurring human prion disease. To better characterize the transcriptional cascades associated with sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, we investigated the global gene expression profile in samples from the frontal cortex of 10 patients with sCJD and 10 non-neurological controls by microarray analysis. The comparison identified 333 highly differentially expressed genes (hDEGs) in sCJD. Functional enrichment Gene Ontology analysis revealed that hDEGs were mainly associated with synaptic transmission, including GABA (q value = 0.049) and glutamate (q value = 0.005) signaling, and the immune/inflammatory response. Furthermore, the analysis of cellular components performed on hDEGs showed a compromised regulation of vesicle-mediated transport with mainly up-regulated genes related to the endosome (q value = 0.01), lysosome (q value = 0.04), and extracellular exosome (q value < 0.01). A targeted analysis of the retromer core component VPS35 (vacuolar protein sorting-associated protein 35) showed a down-regulation of gene expression (p value= 0.006) and reduced brain protein levels (p value= 0.002). Taken together, these results confirm and expand previous microarray expression profile data in sCJD. Most significantly, they also demonstrate the involvement of the endosomal-lysosomal system. Since the latter is a common pathogenic pathway linking together diseases, such as Alzheimer’s and Parkinson’s, it might be the focus of future studies aimed to identify new therapeutic targets in neurodegenerative diseases.
AB - Functional genomics applied to the study of RNA expression profiles identified several abnormal molecular processes in experimental prion disease. However, only a few similar studies have been carried out to date in a naturally occurring human prion disease. To better characterize the transcriptional cascades associated with sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, we investigated the global gene expression profile in samples from the frontal cortex of 10 patients with sCJD and 10 non-neurological controls by microarray analysis. The comparison identified 333 highly differentially expressed genes (hDEGs) in sCJD. Functional enrichment Gene Ontology analysis revealed that hDEGs were mainly associated with synaptic transmission, including GABA (q value = 0.049) and glutamate (q value = 0.005) signaling, and the immune/inflammatory response. Furthermore, the analysis of cellular components performed on hDEGs showed a compromised regulation of vesicle-mediated transport with mainly up-regulated genes related to the endosome (q value = 0.01), lysosome (q value = 0.04), and extracellular exosome (q value < 0.01). A targeted analysis of the retromer core component VPS35 (vacuolar protein sorting-associated protein 35) showed a down-regulation of gene expression (p value= 0.006) and reduced brain protein levels (p value= 0.002). Taken together, these results confirm and expand previous microarray expression profile data in sCJD. Most significantly, they also demonstrate the involvement of the endosomal-lysosomal system. Since the latter is a common pathogenic pathway linking together diseases, such as Alzheimer’s and Parkinson’s, it might be the focus of future studies aimed to identify new therapeutic targets in neurodegenerative diseases.
KW - Genome-wide expression
KW - Human prion
KW - Membrane trafficking
KW - Retromer
KW - Sporadic Creutzfeldt-Jakob disease
KW - VPS35
UR - http://www.scopus.com/inward/record.url?scp=85056669421&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056669421&partnerID=8YFLogxK
U2 - 10.1007/s12035-018-1421-1
DO - 10.1007/s12035-018-1421-1
M3 - Article
C2 - 30446946
AN - SCOPUS:85056669421
JO - Molecular Neurobiology
JF - Molecular Neurobiology
SN - 0893-7648
ER -