| 1. |
- Dibattista, Michele, et al.
(författare)
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The cellular prion protein is expressed in olfactory sensory neurons of adult mice but does not affect the early events of the olfactory transduction pathway
- 2011
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Ingår i: Chemical Senses. - : Oxford University Press. - 0379-864X .- 1464-3553. ; 36:9, s. 791-797
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Tidskriftsartikel (refereegranskat)abstract
- A conformational conversion of the cellular prion protein (PrPC) is now recognized as the causal event of fatal neurodegenerative disorders, known as prion diseases. In spite of long-lasting efforts, however, the physiological role of PrPC remains unclear. It has been reported that PrPC is expressed in various areas of the olfactory system, including the olfactory epithelium, but its precise localization in olfactory sensory neurons (OSNs) is still debated. Here, using immunohistochemistry tools, we have reinvestigated the expression and localization of PrPC in the olfactory epithelium of adult congenic mice expressing different PrPC amounts, that is, wild-type, PrP-knockout, and transgenic PrPC-overexpressing animals. We found that PrPC was expressed in OSNs, in which, however, it was unevenly distributed, being detectable at low levels in cell bodies, dendrites and apical layer, and more abundantly in axons. We also studied the involvement of PrPC in the response of the olfactory epithelium to odorants, by comparing the electro-olfactograms of the 3 mouse lines subjected to different stimulation protocols. We found no significant difference between the 3 PrP genotypes, supporting previous reports that exclude a direct action of PrPC in the early signal transduction activity of the olfactory epithelium.
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| 2. |
- Norante, Rosa Pia, et al.
(författare)
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Generation and validation of novel adeno-associated viral vectors for the analysis of Ca2+ homeostasis in motor neurons
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A finely tuned Ca2+ homeostasis in restricted cell domains is of fundamental importance for neurons, where transient Ca2+ oscillations direct the proper coordination of electro-chemical signals and overall neuronal metabolism. Once such a precise regulation is unbalanced, however, neuronal functions and viability are severely compromised. Accordingly, disturbed Ca2+ metabolism has often been claimed as a major contributor to different neurodegenerative disorders, such as amyotrophic lateral sclerosis that is characterised by selective motor neuron (MN) damage. This notion highlights the need for probes for the specific and precise analysis of local Ca2+ dynamics in MNs. Here, we generated and functionally validated adeno-associated viral vectors for the expression of gene-encoded fluorescent Ca2+ indicators targeted to different cell domains, under the transcriptional control of a MN-specific promoter. We demonstrated that the probes are specifically expressed, and allow reliable local Ca2+ measurements, in MNs from murine primary spinal cord cultures, and can also be expressed in spinal cord MNs in vivo, upon systemic administration to newborn mice. Preliminary analyses using these novel vectors have shown larger cytosolic Ca2+ responses following stimulation of AMPA receptors in the cytosol of primary cultured MNs from a murine genetic model of ALS compared to the healthy counterpart.
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| 3. |
- Peggion, Caterina, et al.
(författare)
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Microglia in Prion Diseases : Angels or Demons?
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 21:20
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Forskningsöversikt (refereegranskat)abstract
- Prion diseases are rare transmissible neurodegenerative disorders caused by the accumulation of a misfolded isoform (PrPSc) of the cellular prion protein (PrP) in the central nervous system (CNS). Neuropathological hallmarks of prion diseases are neuronal loss, astrogliosis, and enhanced microglial proliferation and activation. As immune cells of the CNS, microglia participate both in the maintenance of the normal brain physiology and in driving the neuroinflammatory response to acute or chronic (e.g., neurodegenerative disorders) insults. Microglia involvement in prion diseases, however, is far from being clearly understood. During this review, we summarize and discuss controversial findings, both in patient and animal models, suggesting a neuroprotective role of microglia in prion disease pathogenesis and progression, or-conversely-a microglia-mediated exacerbation of neurotoxicity in later stages of disease. We also will consider the active participation of PrP in microglial functions, by discussing previous reports, but also by presenting unpublished results that support a role for PrP in cytokine secretion by activated primary microglia.
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| 4. |
- Pilotto, Andrea, et al.
(författare)
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Plasma p-tau217 in Alzheimer's disease: Lumipulse and ALZpath SIMOA head-to-head comparison.
- 2024
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Ingår i: medRxiv : the preprint server for health sciences.
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Tidskriftsartikel (refereegranskat)abstract
- Plasma phosphorylated-tau217 (p-tau217) has been shown to be one of the most accurate diagnostic markers for Alzheimer's disease (AD). No studies have compared the clinical performance of p-tau217 as assessed by the fully automated Lumipulse and SIMOA ALZpath p-tau217.To evaluate the diagnostic accuracy of Lumipulse and SIMOA plasma p-tau217 assays for AD.The study included 392 participants, 162 with AD, 70 with other neurodegenerative diseases (NDD) with CSF biomarkers and 160 healthy controls. Plasma p-tau217 levels were measured using the Lumipulse and ALZpath SIMOA assays. The ability of p-tau217 assessed by both techniques to discriminate AD from NDD and controls was investigated using ROC analyses.Both techniques showed high internal consistency of p-tau217 with similar correlation with CSF p-tau181 levels. In head-to-head comparison, Lumipulse and SIMOA showed similar diagnostic accuracy for differentiating AD from NDD (area under the curve [AUC] 0.952, 95%CI 0.927-0.978 vs 0.955, 95%CI 0.928-0.982, respectively) and HC (AUC 0.938, 95%CI 0.910-0.966 and 0.937, 95% CI0.907-0.967 for both assays).This study demonstrated the high precision and diagnostic accuracy of p-tau217 for the clinical diagnosis of Alzheimer's disease using either fully automated or semi-automated techniques.
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| 5. |
- Stella, Roberto, et al.
(författare)
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Relative Quantification of Membrane Proteins in Wild-Type and Prion Protein (PrP)-Knockout Cerebellar Granule Neurons
- 2012
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 11:2, s. 523-536
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 25% of eukaryotic proteins possessing homology to at least two trans membrane domains are predicted to be embedded in biological membranes. Nevertheless, this group of proteins is not usually well represented in proteome-wide experiments due to their refractory nature. Here we present a quantitative mass spectrometry-based comparison of membrane protein expression in cerebellar granule neurons grown in primary culture that were isolated from wild-type mice and mice lacking the cellular prion protein. This protein is a cell-surface glycoprotein that is mainly expressed in the central nervous system and is involved in several neurodegenerative disorders, though its physiological role is unclear. We used a low specificity enzyme a-chymotrypsin to digest membrane proteins preparations that had been separated by SDS-PAGE. The resulting peptides were labeled with tandem mass tags and analyzed by MS. The differentially expressed proteins identified using this approach were further analyzed by multiple reaction monitoring to confirm the expression level changes.
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