Claudio Soto - Academia.edu (original) (raw)
Papers by Claudio Soto
Prions and Diseases, 2012
Prions and Mad Cow Disease, 2003
Current and Emerging Principles and Therapies, 2010
... ZANE MARTIN AND CLAUDIO SOTO Departments of Neurology, Neuroscience and Cell Biology, and Bio... more ... ZANE MARTIN AND CLAUDIO SOTO Departments of Neurology, Neuroscience and Cell Biology, and Biochemistry and Molecular Biology, George and Cynthia Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, Texas ...
Expert Opinion on Drug Discovery, 2009
Neurodegenerative diseases are a group of chronic and progressive disorders of the nervous system... more Neurodegenerative diseases are a group of chronic and progressive disorders of the nervous system. A hallmark event in these diseases is the misfolding and accumulation in the brain of protein aggregates. In this article, we describe the knowledge of the mechanism of protein misfolding and aggregation, its role in neurodegeneration and the diverse therapeutic targets for intervention. We also critically review various strategies under development to discover drugs attacking this process. In spite of the substantial progress on understanding the critical role of protein misfolding and aggregation, drugs effective against this process are still years away from approval.
Frontiers in Medicinal Chemistry - Online, 2004
Protein Design, 2006
Compelling evidence strongly suggests that the conversion of a normal soluble protein into a beta... more Compelling evidence strongly suggests that the conversion of a normal soluble protein into a beta-sheet-rich oligomeric structure and further fibril formation is the critical step in the pathogenesis of several human diseases, termed protein misfolding disorders. Therefore, a promising therapeutic strategy consists of the design of molecules that prevent the misfolding and aggregation of these proteins. In this chapter, we survey the mechanism of protein misfolding and some strategies to rationally produce inhibitors of this process.
Current Hypotheses and Research Milestones in Alzheimer's Disease, 2009
Amyloid Proteins, 2004
Summary Diverse human disorders, including most neurodegenerative diseases, are thought to arise ... more Summary Diverse human disorders, including most neurodegenerative diseases, are thought to arise from the misfolding and aggregation of an underlying protein. We have recently described a novel technology to amplify cyclically the misfolding and aggregation ...
Techniques in Prion Research, 2004
Pharmacological Mechanisms in Alzheimer's Therapeutics, 2007
... Christie, & Karran, 1998), small sulfonated anions (Kisilevsky et al., 1995),... more ... Christie, & Karran, 1998), small sulfonated anions (Kisilevsky et al., 1995), amphiphilic surfactants, such as di-C6-PC and di-C7-PC (Wang, Chen, & Chou, 2005), wine polyphenols and ... Dewachter, I., Van Dorpe, J., Spittaels, K., Tesseur, I., Van den, HC, Moechars, D., et al. ...
International Journal of Cell Biology, 2013
The misfolding, aggregation, and tissue accumulation of proteins are common events in diverse chr... more The misfolding, aggregation, and tissue accumulation of proteins are common events in diverse chronic diseases, known as protein misfolding disorders. Many of these diseases are associated with aging, but the mechanism for this connection is unknown. Recent evidence has shown that the formation and accumulation of protein aggregates may be a process frequently occurring during normal aging, but it is unknown whether protein misfolding is a cause or a consequence of aging. To combat the formation of these misfolded aggregates cells have developed complex and complementary pathways aiming to maintain protein homeostasis. These protective pathways include the unfolded protein response, the ubiquitin proteasome system, autophagy, and the encapsulation of damaged proteins in aggresomes. In this paper we review the current knowledge on the role of protein misfolding in disease and aging as well as the implication of deficiencies in the proteostasis cellular pathways in these processes. It is likely that further understanding of the mechanisms involved in protein misfolding and the natural defense pathways may lead to novel strategies for treatment of age-dependent protein misfolding disorders and perhaps aging itself.
Virus Research, 2015
Recent findings have shown that several misfolded proteins can transmit disease pathogenesis in a... more Recent findings have shown that several misfolded proteins can transmit disease pathogenesis in a prion-like manner by transferring their conformational properties to normally folded units. However, the extent by which these molecule-to-molecule or cell-to-cell spreading processes reflect the entire prion behavior is now subject of controversy, especially due to the lack of epidemiological data supporting inter-individual transmission of non-prion protein misfolding diseases. Nevertheless, extensive research has shown that several of the typical characteristics of prions can be observed for Aβ and tau aggregates when administered in animal models. In this article we review recent studies describing the prion-like features of both proteins, highlighting the similarities with bona fide prions in terms of inter-individual transmission, their strain-like conformational diversity, and the transmission of misfolded aggregates by different routes of administration.
Neurodegeneration and Prion Disease, 2005
Cells can die by diverse mechanisms depending upon the stimulus triggering the death process. Amo... more Cells can die by diverse mechanisms depending upon the stimulus triggering the death process. Among these mechanisms it is possible to include necrosis, apoptosis, autophagia, mitotic catastrophe, and others1, 2. Apoptosis has been implicated in diseases affecting ...
Current Hypotheses and Research Milestones in Alzheimer's Disease, 2009
Misfolding and aggregation of proteins is the main feature of a group of maladies which include m... more Misfolding and aggregation of proteins is the main feature of a group of maladies which include most of neurodegenerative diseases (such as Alzheimer's, Parkinson's, Huntington's, and prion diseases), as well as several systemic amyloidosis. Among them, ...
Methods in Molecular Biology, 2012
Microbial Food Contamination, Second Edition, 2007
Alzheimer's & Dementia, 2014
Background: The major pathological protein in frontotemporal dementia and motor neuron disease is... more Background: The major pathological protein in frontotemporal dementia and motor neuron disease is T ransactive response D NA-binding Protein of 43 kDa . Similar to tau, pathological TDP-43 becomes hyperphosphorylated and is present in neuronal inclusions. Recently, TDP-43 aggregation has also been described in up to 50% of sporadic Alzheimer's disease cases. We describe an accumulation of endogenous phosophorylated TDP-43 in APP/PS1 mice. We investigated whether increased expression of TDP-43 accelerates the pathological outcome in an APP/PS1 background. Methods: We utilized a cell-specific inducible model to selectively drive expression of TDP-43 in the cortex and hippocampus in an APP/PS1 background (tet-off). Results: What we observed from this model at eight to nine months of age was an increase in phosphorylated TDP-43. Interestingly, there was also a distinct change in the pattern of plaque deposition inlitter mates expressing TDP-43. Conclusions: This model of TDP-43 expression could provide insight into understanding mechanisms associated with plaque deposition and/or APP processing.
Biochemical and Biophysical Research Communications, 1997
The inheritance of the apolipoprotein (apo) E4 allele is an important risk factor for late-onset ... more The inheritance of the apolipoprotein (apo) E4 allele is an important risk factor for late-onset Alzheimer's disease (AD). A major component of the Alzheimer's disease neuritic plaques is amyloid beta (A beta). We previously identified apoE/A beta complexes within neuritic plaques (1). It was not known if this interaction takes place before or after A beta peptides become incorporated into neuritic plaques. To address this question we sought evidence of apoE complexes with brain soluble A beta peptides in AD and control patients. In addition, numerous proteins have been shown to bind A beta peptides in vitro. It is not know if any of these bind brain sA beta in vivo. We found evidence for the presence of apoE/dimeric sA beta complexes in the AD brain and could not detect complexes with other A beta peptide binding proteins. The binding of sA beta to apoE may be one factor influencing its clearance from the brain and/or its conformational state.
Nature Reviews Microbiology, 2004
| Prion diseases are among the most intriguing infectious diseases and are associated with unconv... more | Prion diseases are among the most intriguing infectious diseases and are associated with unconventional proteinaceous infectious agents known as prions. Prions seem to lack nucleic acid and propagate by transmission of protein misfolding. The nature of prions and their unique mode of transmission present challenges for early diagnosis of prion diseases. In this article, state-of-the-art prion diagnostic techniques, together with the new strategies that are being used to develop sensitive, early and non-invasive diagnoses for these diseases are reviewed.
Prions and Diseases, 2012
Prions and Mad Cow Disease, 2003
Current and Emerging Principles and Therapies, 2010
... ZANE MARTIN AND CLAUDIO SOTO Departments of Neurology, Neuroscience and Cell Biology, and Bio... more ... ZANE MARTIN AND CLAUDIO SOTO Departments of Neurology, Neuroscience and Cell Biology, and Biochemistry and Molecular Biology, George and Cynthia Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, Texas ...
Expert Opinion on Drug Discovery, 2009
Neurodegenerative diseases are a group of chronic and progressive disorders of the nervous system... more Neurodegenerative diseases are a group of chronic and progressive disorders of the nervous system. A hallmark event in these diseases is the misfolding and accumulation in the brain of protein aggregates. In this article, we describe the knowledge of the mechanism of protein misfolding and aggregation, its role in neurodegeneration and the diverse therapeutic targets for intervention. We also critically review various strategies under development to discover drugs attacking this process. In spite of the substantial progress on understanding the critical role of protein misfolding and aggregation, drugs effective against this process are still years away from approval.
Frontiers in Medicinal Chemistry - Online, 2004
Protein Design, 2006
Compelling evidence strongly suggests that the conversion of a normal soluble protein into a beta... more Compelling evidence strongly suggests that the conversion of a normal soluble protein into a beta-sheet-rich oligomeric structure and further fibril formation is the critical step in the pathogenesis of several human diseases, termed protein misfolding disorders. Therefore, a promising therapeutic strategy consists of the design of molecules that prevent the misfolding and aggregation of these proteins. In this chapter, we survey the mechanism of protein misfolding and some strategies to rationally produce inhibitors of this process.
Current Hypotheses and Research Milestones in Alzheimer's Disease, 2009
Amyloid Proteins, 2004
Summary Diverse human disorders, including most neurodegenerative diseases, are thought to arise ... more Summary Diverse human disorders, including most neurodegenerative diseases, are thought to arise from the misfolding and aggregation of an underlying protein. We have recently described a novel technology to amplify cyclically the misfolding and aggregation ...
Techniques in Prion Research, 2004
Pharmacological Mechanisms in Alzheimer's Therapeutics, 2007
... Christie, & Karran, 1998), small sulfonated anions (Kisilevsky et al., 1995),... more ... Christie, & Karran, 1998), small sulfonated anions (Kisilevsky et al., 1995), amphiphilic surfactants, such as di-C6-PC and di-C7-PC (Wang, Chen, & Chou, 2005), wine polyphenols and ... Dewachter, I., Van Dorpe, J., Spittaels, K., Tesseur, I., Van den, HC, Moechars, D., et al. ...
International Journal of Cell Biology, 2013
The misfolding, aggregation, and tissue accumulation of proteins are common events in diverse chr... more The misfolding, aggregation, and tissue accumulation of proteins are common events in diverse chronic diseases, known as protein misfolding disorders. Many of these diseases are associated with aging, but the mechanism for this connection is unknown. Recent evidence has shown that the formation and accumulation of protein aggregates may be a process frequently occurring during normal aging, but it is unknown whether protein misfolding is a cause or a consequence of aging. To combat the formation of these misfolded aggregates cells have developed complex and complementary pathways aiming to maintain protein homeostasis. These protective pathways include the unfolded protein response, the ubiquitin proteasome system, autophagy, and the encapsulation of damaged proteins in aggresomes. In this paper we review the current knowledge on the role of protein misfolding in disease and aging as well as the implication of deficiencies in the proteostasis cellular pathways in these processes. It is likely that further understanding of the mechanisms involved in protein misfolding and the natural defense pathways may lead to novel strategies for treatment of age-dependent protein misfolding disorders and perhaps aging itself.
Virus Research, 2015
Recent findings have shown that several misfolded proteins can transmit disease pathogenesis in a... more Recent findings have shown that several misfolded proteins can transmit disease pathogenesis in a prion-like manner by transferring their conformational properties to normally folded units. However, the extent by which these molecule-to-molecule or cell-to-cell spreading processes reflect the entire prion behavior is now subject of controversy, especially due to the lack of epidemiological data supporting inter-individual transmission of non-prion protein misfolding diseases. Nevertheless, extensive research has shown that several of the typical characteristics of prions can be observed for Aβ and tau aggregates when administered in animal models. In this article we review recent studies describing the prion-like features of both proteins, highlighting the similarities with bona fide prions in terms of inter-individual transmission, their strain-like conformational diversity, and the transmission of misfolded aggregates by different routes of administration.
Neurodegeneration and Prion Disease, 2005
Cells can die by diverse mechanisms depending upon the stimulus triggering the death process. Amo... more Cells can die by diverse mechanisms depending upon the stimulus triggering the death process. Among these mechanisms it is possible to include necrosis, apoptosis, autophagia, mitotic catastrophe, and others1, 2. Apoptosis has been implicated in diseases affecting ...
Current Hypotheses and Research Milestones in Alzheimer's Disease, 2009
Misfolding and aggregation of proteins is the main feature of a group of maladies which include m... more Misfolding and aggregation of proteins is the main feature of a group of maladies which include most of neurodegenerative diseases (such as Alzheimer's, Parkinson's, Huntington's, and prion diseases), as well as several systemic amyloidosis. Among them, ...
Methods in Molecular Biology, 2012
Microbial Food Contamination, Second Edition, 2007
Alzheimer's & Dementia, 2014
Background: The major pathological protein in frontotemporal dementia and motor neuron disease is... more Background: The major pathological protein in frontotemporal dementia and motor neuron disease is T ransactive response D NA-binding Protein of 43 kDa . Similar to tau, pathological TDP-43 becomes hyperphosphorylated and is present in neuronal inclusions. Recently, TDP-43 aggregation has also been described in up to 50% of sporadic Alzheimer's disease cases. We describe an accumulation of endogenous phosophorylated TDP-43 in APP/PS1 mice. We investigated whether increased expression of TDP-43 accelerates the pathological outcome in an APP/PS1 background. Methods: We utilized a cell-specific inducible model to selectively drive expression of TDP-43 in the cortex and hippocampus in an APP/PS1 background (tet-off). Results: What we observed from this model at eight to nine months of age was an increase in phosphorylated TDP-43. Interestingly, there was also a distinct change in the pattern of plaque deposition inlitter mates expressing TDP-43. Conclusions: This model of TDP-43 expression could provide insight into understanding mechanisms associated with plaque deposition and/or APP processing.
Biochemical and Biophysical Research Communications, 1997
The inheritance of the apolipoprotein (apo) E4 allele is an important risk factor for late-onset ... more The inheritance of the apolipoprotein (apo) E4 allele is an important risk factor for late-onset Alzheimer's disease (AD). A major component of the Alzheimer's disease neuritic plaques is amyloid beta (A beta). We previously identified apoE/A beta complexes within neuritic plaques (1). It was not known if this interaction takes place before or after A beta peptides become incorporated into neuritic plaques. To address this question we sought evidence of apoE complexes with brain soluble A beta peptides in AD and control patients. In addition, numerous proteins have been shown to bind A beta peptides in vitro. It is not know if any of these bind brain sA beta in vivo. We found evidence for the presence of apoE/dimeric sA beta complexes in the AD brain and could not detect complexes with other A beta peptide binding proteins. The binding of sA beta to apoE may be one factor influencing its clearance from the brain and/or its conformational state.
Nature Reviews Microbiology, 2004
| Prion diseases are among the most intriguing infectious diseases and are associated with unconv... more | Prion diseases are among the most intriguing infectious diseases and are associated with unconventional proteinaceous infectious agents known as prions. Prions seem to lack nucleic acid and propagate by transmission of protein misfolding. The nature of prions and their unique mode of transmission present challenges for early diagnosis of prion diseases. In this article, state-of-the-art prion diagnostic techniques, together with the new strategies that are being used to develop sensitive, early and non-invasive diagnoses for these diseases are reviewed.