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Pierluigi Gambetti

Bio: Pierluigi Gambetti is an academic researcher. The author has contributed to research in topics: Transmissible spongiform encephalopathy. The author has an hindex of 1, co-authored 1 publications receiving 285 citations.

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Book
01 Jan 2013
TL;DR: The author examines the role of Cellular Prion Protein in the Amyloid-ss Oligomer Pathophysiology of Alzheimer's Disease, as well as modeling the Cell Biology of Prions and Yeast Prions.
Abstract: Chapter 1 Transmissible Spongiform Encephalopathy: from the High Middle Ages to Daniel Carlton Gajdusek Paul Brown Chapter 2 The Rich Chemistry of the Copper and Zinc Sites in Cellular Prion Protein Glenn L. Millhauser Chapter 3 Role of Cellular Prion Protein in the Amyloid-ss Oligomer Pathophysiology of Alzheimer's Disease Adam C. Kaufman, Stephen M. Strittmatter Chapter 4 Cellular Prion Protein and Cancers Wei Xin, Man-sun Sy, Chaoyang Li Chapter 5 Insoluble Cellular Prion Protein Wen-Quan Zou Chapter 6 Protein Misfolding Cyclic Amplification Fabio Moda, Sandra Pritzkow, Claudio Soto Chapter 7 Cofactor Involvement in Prion Propagation Surachai Supattapone, Michael B. Miller Chapter 8 Prion Protein Conversion and Lipids Jiyan Ma Chapter 9 New Perspectives on Prion Conversion: Introducing a Mechanism of Deformed Templating Ilia V. Baskakov Chapter 10 Infectious and Pathogenic Forms of Prion Protein Emiliano Biasini, David A. Harris Chapter 11 Cellular Mechanisms of Propagation and Clearance Hermann M. Schatzl Chapter 12 Molecular Mechanisms Encoding Quantitative and Qualitative Traits of Prion Strains Jiri G. Safar Chapter 13 Modeling the Cell Biology of Prions Richard Rubenstein, Robert B. Petersen Chapter 14 Prion Strain Interference Charles R. Schutt, Ronald A. Shikiya, Jason C. Bartz Chapter 15 Introduction to Yeast and Fungal Prions Reed B. Wickner Chapter 16 Yeast Prions are Pathogenic, in-register Parallel Amyloids Reed B. Wickner, Herman K. Edskes, David A. Bateman, Amy C. Kelly, Anton Gorkovskiy

382 citations


Cited by
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Journal ArticleDOI
TL;DR: The review will emphasize the molecular mechanisms useful for the development of therapeutic strategies that are based on modulating ROS levels to treat cancer, and report on the growing data that highlight the role of ROS generated by different metabolic pathways as Trojan horses to eliminate cancer cells.
Abstract: Reactive oxygen species (ROS) constitute a group of highly reactive molecules that have evolved as regulators of important signaling pathways. It is now well accepted that moderate levels of ROS are required for several cellular functions, including gene expression. The production of ROS is elevated in tumor cells as a consequence of increased metabolic rate, gene mutation and relative hypoxia, and excess ROS are quenched by increased antioxidant enzymatic and nonenzymatic pathways in the same cells. Moderate increases of ROS contribute to several pathologic conditions, among which are tumor promotion and progression, as they are involved in different signaling pathways and induce DNA mutation. However, ROS are also able to trigger programmed cell death (PCD). Our review will emphasize the molecular mechanisms useful for the development of therapeutic strategies that are based on modulating ROS levels to treat cancer. Specifically, we will report on the growing data that highlight the role of ROS generated by different metabolic pathways as Trojan horses to eliminate cancer cells.

1,004 citations

Journal ArticleDOI
TL;DR: Oxidative stress seems to be mainly driven by inflammation and oxidative burst in microglia; however, its effects might be amplified in patients with progressive MS by age-dependent iron accumulation in the brain and by mitochondrial gene deletions, triggered by the chronic inflammatory process.
Abstract: Major progress has been made during the past three decades in understanding the inflammatory process and pathogenetic mechanisms in multiple sclerosis (MS). Consequently, effective anti-inflammatory and immunomodulatory treatments are now available for patients in the relapsing-remitting stage of the disease. This Review summarizes studies on the pathology of progressive MS and discusses new data on the mechanisms underlying its pathogenesis. In progressive MS, as in relapsing-remitting MS, active tissue injury is associated with inflammation, but the inflammatory response in the progressive phase occurs at least partly behind the blood-brain barrier, which makes it more difficult to treat. The other mechanisms that drive disease in patients with primary or secondary progressive MS are currently unresolved, although oxidative stress resulting in mitochondrial injury might participate in the induction of demyelination and neurodegeneration in both the relapsing-remitting and progressive stages of MS. Oxidative stress seems to be mainly driven by inflammation and oxidative burst in microglia; however, its effects might be amplified in patients with progressive MS by age-dependent iron accumulation in the brain and by mitochondrial gene deletions, triggered by the chronic inflammatory process.

801 citations

Journal ArticleDOI
TL;DR: Current and investigational drugs that modulate SLC transporters, as well as promising drug targets, are highlighted.
Abstract: Solute carrier (SLC) transporters - a family of more than 300 membrane-bound proteins that facilitate the transport of a wide array of substrates across biological membranes - have important roles in physiological processes ranging from the cellular uptake of nutrients to the absorption of drugs and other xenobiotics. Several classes of marketed drugs target well-known SLC transporters, such as neurotransmitter transporters, and human genetic studies have provided powerful insight into the roles of more-recently characterized SLC transporters in both rare and common diseases, indicating a wealth of new therapeutic opportunities. This Review summarizes knowledge on the roles of SLC transporters in human disease, describes strategies to target such transporters, and highlights current and investigational drugs that modulate SLC transporters, as well as promising drug targets.

541 citations

Journal ArticleDOI
TL;DR: Treatments that target calcitonin gene-related peptide (CGRP) and its receptor are proving effective for migraine treatment, and the hypothesis that CGRP has a major role in migraine pathophysiology is strongly supported.
Abstract: Treatment of migraine is on the cusp of a new era with the development of drugs that target the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) or its receptor. Several of these drugs are expected to receive approval for use in migraine headache in 2018 and 2019. CGRP-related therapies offer considerable improvements over existing drugs as they are the first to be designed specifically to act on the trigeminal pain system, they are more specific and they seem to have few or no adverse effects. CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. As these drugs come into clinical use, we provide an overview of knowledge that has led to successful development of these drugs. We describe the biology of CGRP signalling, summarize key clinical evidence for the role of CGRP in migraine headache, including the efficacy of CGRP-targeted treatment, and synthesize what is known about the role of CGRP in the trigeminovascular system. Finally, we consider how the latest findings provide new insight into the central role of the trigeminal ganglion in the pathophysiology of migraine.

536 citations

Journal ArticleDOI
TL;DR: The shared mechanisms of inflammation, oxidative stress, common metabolites and endothelial dysfunction that characterize the aetiologies of OA and MetS are summarized, and metabolic OA is nominated as the fifth component of MetS.
Abstract: Metabolic osteoarthritis (OA) has now been characterized as a subtype of OA, and links have been discovered between this phenotype and metabolic syndrome (MetS)--both with individual MetS components and with MetS as a whole. Hypertension associates with OA through subchondral ischaemia, which can compromise nutrient exchange into articular cartilage and trigger bone remodelling. Ectopic lipid deposition in chondrocytes induced by dyslipidemia might initiate OA development, exacerbated by deregulated cellular lipid metabolism in joint tissues. Hyperglycaemia and OA interact at both local and systemic levels; local effects of oxidative stress and advanced glycation end-products are implicated in cartilage damage, whereas low-grade systemic inflammation results from glucose accumulation and contributes to a toxic internal environment that can exacerbate OA. Obesity-related metabolic factors, particularly altered levels of adipokines, contribute to OA development by inducing the expression of proinflammatory factors as well as degradative enzymes, leading to the inhibition of cartilage matrix synthesis and stimulation of subchondral bone remodelling. In this Review, we summarize the shared mechanisms of inflammation, oxidative stress, common metabolites and endothelial dysfunction that characterize the aetiologies of OA and MetS, and nominate metabolic OA as the fifth component of MetS. We also describe therapeutic opportunities that might arise from uniting these concepts.

422 citations