{"title":"Getting in Shape: Targeting the Etiology of Protein Misfolding Diseases – Celebrating Jeffery Kelly's Pioneering Work","authors":"Lars Plate, Joseph C. Genereux","doi":"10.1002/ijch.202481231","DOIUrl":"https://doi.org/10.1002/ijch.202481231","url":null,"abstract":"<p>We are excited to share this special issue dedicated to Jeffery Kelly, commemorating his 2023 Wolf Prize in Chemistry. This award recognizes his pioneering research accomplishments, which have dramatically changed our fundamental understanding of how proteins (mis)fold in vitro and in vivo while at the same time leveraging those discoveries to change the lives of patients across the globe. The award specifically refers to the latter: “for developing a clinical strategy to ameliorate pathological protein aggregation”. This is exemplified by the development of Tafamidis,<span><sup>1</sup></span> the first clinically approved molecule to treat a disease of protein misfolding.<span><sup>2, 3</sup></span></p><p>Jeff's discovery that protein misfolding of transthyretin (TTR) is an obligate step prior to protein aggregation<span><sup>4</sup></span> established that preventing the accumulation of misfolded proteins can block disease pathology. Rigorous biochemical and biophysical characterization established that transthyretin tetramer dissociation into monomers is the rate-limiting step that initiates protein misfolding.<span><sup>5</sup></span> This critical insight motivated the development of small molecules that could stabilize the native conformation of TTR,<span><sup>6</sup></span> culminating in the development and clinical approval of Tafamidis.</p><p>Later, Jeff and his collaborators introduced the idea of protein homeostasis (or proteostasis).<span><sup>7</sup></span> Protein folding and maturation into its native structure is not only governed by the intrinsic stability of each polypeptide chain, but in a cellular environment, the large ensemble of molecular chaperones, co-chaperones, other protein quality factors, and their interacting activities maintain the integrity of the proteome for cellular and organismal health. Importantly, dysregulation of the proteostasis network can lead to insufficient protein folding capacity and accumulation of misfolded proteins, which is associated with various disease states, ranging from neurodegeneration to diabetes and cancer.<span><sup>8, 9</sup></span></p><p>Several reviews and articles in this special issue address how a detailed understanding of protein misfolding and the proteostasis network can be leveraged in therapeutic development. These contributions highlight the impact that Jeff's work has had on the broader chemistry and biology research community.</p><p>Although transthyretin amyloidosis was once thought to be rare, we now know that millions of people are carriers of likely pathogenic variants.<span><sup>10</sup></span> Following the success of Tafamidis, there are now many emerging approaches for therapeutic intervention in this disease class, as reviewed by Per Hammarström in this issue.<span><sup>11</sup></span> Another class of protein associated with systemic amyloidosis is immunoglobulin light chain, which lead to AL amyloidosis. Gareth Morgan reviews how both amyloidogenicity and ","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 12","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202481231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cover Picture: (Isr. J. Chem. 12/2024)","authors":"","doi":"10.1002/ijch.202481201","DOIUrl":"https://doi.org/10.1002/ijch.202481201","url":null,"abstract":"<p>The cover art depicts Jeffery Kelly's pioneering development of Tafamidis as a clinical strategy to ameliorate transthyretin protein aggregation (in the center). Surrounding images highlight examples from this special issue of how his work has influenced other approaches to characterize and target the etiology of diverse protein misfolding diseases.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 12","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202481201","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cover Picture: (Isr. J. Chem. 10-11/2024)","authors":"","doi":"10.1002/ijch.202481001","DOIUrl":"https://doi.org/10.1002/ijch.202481001","url":null,"abstract":"<p>The cover image shows the logo of the 15th International Conference on Quasicrystals, held at Tel Aviv University in June 2023. The logo depicts the hexagonal Star of David. The background depicts a hexagonal quasiperiodic tiling, whose construction and characterization are the focus of the Review by Coates et al. in this volume. Such aperiodic yet perfectly ordered trigonal and hexagonal tilings served to study various experimental systems, such as the 3-fold surfaces of icosahedral quasicrystals and 6-fold bilayer graphene.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 10-11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202481001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Topological Quantum Numbers in Quasicrystals","authors":"Johannes Kellendonk","doi":"10.1002/ijch.202400027","DOIUrl":"https://doi.org/10.1002/ijch.202400027","url":null,"abstract":"<p>We provide an overview on the theory of topological quantum numbers from the point of view of non-commutative topology. Topological phases are described by <i>K</i>-groups of <i>C</i>*-algebras. The algebras are constructed from the set of positions of the nuclei of the materials we want to study. Topological quantum numbers are Chern numbers of <i>K</i>-group elements. Maps between <i>K</i>-groups which are of algebraic topological origin provide the means to obtain relations between different topological quantum numbers as, for instance, in the bulk edge correspondence. We present simple aperiodic examples related to quasicrystals to illustrate the theory.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 10-11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142860946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent Advances in Quasicrystal Research","authors":"Ron Lifshitz","doi":"10.1002/ijch.202412000","DOIUrl":"https://doi.org/10.1002/ijch.202412000","url":null,"abstract":"<p>The study of quasicrystals – materials that are characterized by their aperiodic yet long-range ordered structures<span><sup>1-5</sup></span> – continues to evolve, offering new challenges and opportunities in understanding complex-ordered systems that transcend traditional crystallography. They have emerged as a rich interdisciplinary field, encompassing mathematics, physics, chemistry, and materials science. This introduces the additional challenge of bridging varied research communities, each with its distinct language and culture. Central to the investigation of quasicrystals are mathematical tools that describe their intricate geometric and topological properties, physical models that capture their unique electronic and other physical properties, as well as innovative experimental methods that can be employed to analyze their unique and complex nature. This special issue of the <i>Israel Journal of Chemistry</i> is dedicated to the latest advancements in quasicrystal research, presented at ICQ15 – the <i>15th International Conference on Quasicrystals</i> – held on the campus of Tel Aviv University in June 2023 (see Fig. 1 for a group photo). It offers a valuable snapshot of the current state of quasicrystal research, highlighting the progress made in recent years and the challenges that lie ahead. The collection of Reviews and Research Articles, included here, spans a broad spectrum of topics, reflecting the diverse and interdisciplinary nature of quasicrystal research, providing a good entry point, as well as some deep insight, into the theoretical, experimental and practical underpinnings of aperiodic long-range order.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 10-11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202412000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142860520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Substitutions and their Generalisations","authors":"Neil Mañibo","doi":"10.1002/ijch.202300159","DOIUrl":"https://doi.org/10.1002/ijch.202300159","url":null,"abstract":"<p>Tilings and point sets arising from substitutions are classical mathematical models of quasicrystals. Their hierarchical structure allows one to obtain concrete answers regarding spectral questions tied to the underlying measures and potentials. In this review, we present some generalisations of substitutions, with a focus on substitutions on compact alphabets, and with an outlook towards their spectral theory. Guided by two main examples, we will illustrate what changes when one moves from finite to compact (infinite) alphabets, and discuss under which assumptions do we recover the usual geometric and statistical properties which make them viable models of materials with almost periodic order. We also present a planar example (which is a two-dimensional generalisation of the Thue−Morse substitution), whose diffraction is purely singular continuous.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 10-11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pure Point Diffraction and Almost Periodicity","authors":"Daniel Lenz, Timo Spindeler, Nicolae Strungaru","doi":"10.1002/ijch.202300158","DOIUrl":"https://doi.org/10.1002/ijch.202300158","url":null,"abstract":"<p>This article deals with pure point diffraction and its connection to various notions of almost periodicity. We explain why the Fibonacci chain does not fit into the classical concept of Bohr almost periodicity and how it fits into the classes of mean, Besicovitch and Weyl almost periodic point sets. We report on recent results which characterize pure point diffraction as mean almost periodicity of the underlying structure, and discuss how the complex amplitudes fit into this picture.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 10-11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Profiling the Misfolded Proteome in Human Disease","authors":"Vivian C. Onwudiwe, Joseph C. Genereux","doi":"10.1002/ijch.202300131","DOIUrl":"https://doi.org/10.1002/ijch.202300131","url":null,"abstract":"<p>Changes in protein homeostasis are broadly implicated in many disease states, including amyloidoses, neurodegenerative diseases, cancer, and normal aging. Although this relationship has been fruitful for identifying and developing therapeutic strategies, it is challenging to identify which proteins are misfolding. New technologies have recently emerged that enable proteome-wide interrogation of protein conformation and stability. In this review, we describe these technologies, and how they have been used to identify proteins whose folding changes between disease states. We discuss some of the challenges in this emerging field, and the potential for misfolded protein profiling to provide insight into human disease.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 12","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143186931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unravelling Disorder in Aperiodic Crystals – Diffuse Scattering and Atomic Resolution Holography","authors":"J. R. Stellhorn, E. G. Meekel, A. Minelli","doi":"10.1002/ijch.202300154","DOIUrl":"https://doi.org/10.1002/ijch.202300154","url":null,"abstract":"<p>The atomic-scale disorder of aperiodic crystals, and quasicrystals in particular, is inherently difficult to explore by experimental methods due to their complex atomic arrangements. Two advanced characterization techniques, a revived and an emerging one, offer direct experimental access even to such complex atomic structures: Diffuse Scattering and Atomic Resolution Holography. In this overview, we introduce their specific application to aperiodic crystals and discuss their merits and difficulties.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 10-11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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