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A Lipid-Raft Theory of Alzheimer's Disease. 阿尔茨海默病的脂质筏理论
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2024-10-30 DOI: 10.1146/annurev-biochem-052024-115455
Ari Rappoport
{"title":"A Lipid-Raft Theory of Alzheimer's Disease.","authors":"Ari Rappoport","doi":"10.1146/annurev-biochem-052024-115455","DOIUrl":"https://doi.org/10.1146/annurev-biochem-052024-115455","url":null,"abstract":"<p><p>I present a theory of Alzheimer's disease (AD) that explains its symptoms, pathology, and risk factors. To do this, I introduce a new theory of brain plasticity that elucidates the physiological roles of AD-related agents. New events generate synaptic and branching candidates competing for long-term enhancement. Competition resolution crucially depends on the formation of membrane lipid rafts, which requires astrocyte-produced cholesterol. Sporadic AD is caused by impaired formation of plasma-membrane lipid rafts, preventing the conversion of short- to long-term memory and yielding excessive tau phosphorylation, intracellular cholesterol accumulation, synaptic dysfunction, and neurodegeneration. Amyloid β (Aβ) production is promoted by cholesterol during the switch to competition resolution, and cholesterol accumulation stimulates chronic Aβ production, secretion, and aggregation. The theory addresses all of the major established facts known about the disease and is supported by strong evidence.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":null,"pages":null},"PeriodicalIF":12.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inositol Pyrophosphates as Versatile Metabolic Messengers. 作为多功能代谢信使的肌醇焦磷酸盐
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2024-08-01 DOI: 10.1146/annurev-biochem-030222-121901
Latika Nagpal, Sining He, Feng Rao, Solomon H Snyder
{"title":"Inositol Pyrophosphates as Versatile Metabolic Messengers.","authors":"Latika Nagpal, Sining He, Feng Rao, Solomon H Snyder","doi":"10.1146/annurev-biochem-030222-121901","DOIUrl":"https://doi.org/10.1146/annurev-biochem-030222-121901","url":null,"abstract":"<p><p>Discovered in 1993, inositol pyrophosphates are evolutionarily conserved signaling metabolites whose versatile modes of action are being increasingly appreciated. These include their emerging roles as energy regulators, phosphodonors, steric/allosteric regulators, and G protein-coupled receptor messengers. Through studying enzymes that metabolize inositol pyrophosphates, progress has also been made in elucidating the various cellular and physiological functions of these pyrophosphate-containing, energetic molecules. The two main forms of inositol pyrophosphates, 5-IP<sub>7</sub> and IP<sub>8</sub>, synthesized respectively by inositol-hexakisphosphate kinases (IP6Ks) and diphosphoinositol pentakisphosphate kinases (PPIP5Ks), regulate phosphate homeostasis, ATP synthesis, and several other metabolic processes ranging from insulin secretion to cellular energy utilization. Here, we review the current understanding of the catalytic and regulatory mechanisms of IP6Ks and PPIP5Ks, as well as their counteracting phosphatases. We also highlight the genetic and cellular evidence implicating inositol pyrophosphates as essential mediators of mammalian metabolic homeostasis.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":null,"pages":null},"PeriodicalIF":12.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Nicotinic Acetylcholine Receptor and Its Pentameric Homologs: Toward an Allosteric Mechanism of Signal Transduction at the Atomic Level. 烟碱乙酰胆碱受体及其五聚体同源物：在原子水平上实现信号转导的异构机制。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2024-08-01 Epub Date: 2024-07-02 DOI: 10.1146/annurev-biochem-030122-033116
Marco Cecchini, Pierre-Jean Corringer, Jean-Pierre Changeux
{"title":"The Nicotinic Acetylcholine Receptor and Its Pentameric Homologs: Toward an Allosteric Mechanism of Signal Transduction at the Atomic Level.","authors":"Marco Cecchini, Pierre-Jean Corringer, Jean-Pierre Changeux","doi":"10.1146/annurev-biochem-030122-033116","DOIUrl":"10.1146/annurev-biochem-030122-033116","url":null,"abstract":"<p><p>The nicotinic acetylcholine receptor has served, since its biochemical identification in the 1970s, as a model of an allosteric ligand-gated ion channel mediating signal transition at the synapse. In recent years, the application of X-ray crystallography and high-resolution cryo-electron microscopy, together with molecular dynamic simulations of nicotinic receptors and homologs, have opened a new era in the understanding of channel gating by the neurotransmitter. They reveal, at atomic resolution, the diversity and flexibility of the multiple ligand-binding sites, including recently discovered allosteric modulatory sites distinct from the neurotransmitter orthosteric site, and the conformational dynamics of the activation process as a molecular switch linking these multiple sites. The model emerging from these studies paves the way for a new pharmacology based, first, upon the occurrence of an original mode of indirect allosteric modulation, distinct from a steric competition for a single and rigid binding site, and second, the design of drugs that specifically interact with privileged conformations of the receptor such as agonists, antagonists, and desensitizers. Research on nicotinic receptors is still at the forefront of understanding the mode of action of drugs on the nervous system.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":null,"pages":null},"PeriodicalIF":12.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Signaling from RAS to RAF: The Molecules and Their Mechanisms. 从 RAS 到 RAF 的信号传递：分子及其机制。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2024-08-01 Epub Date: 2024-07-02 DOI: 10.1146/annurev-biochem-052521-040754
Hyesung Jeon, Emre Tkacik, Michael J Eck
{"title":"Signaling from RAS to RAF: The Molecules and Their Mechanisms.","authors":"Hyesung Jeon, Emre Tkacik, Michael J Eck","doi":"10.1146/annurev-biochem-052521-040754","DOIUrl":"10.1146/annurev-biochem-052521-040754","url":null,"abstract":"<p><p>RAF family protein kinases are a key node in the RAS/RAF/MAP kinase pathway, the signaling cascade that controls cellular proliferation, differentiation, and survival in response to engagement of growth factor receptors on the cell surface. Over the past few years, structural and biochemical studies have provided new understanding of RAF autoregulation, RAF activation by RAS and the SHOC2 phosphatase complex, and RAF engagement with HSP90-CDC37 chaperone complexes. These studies have important implications for pharmacologic targeting of the pathway. They reveal RAF in distinct regulatory states and show that the functional RAF switch is an integrated complex of RAF with its substrate (MEK) and a 14-3-3 dimer. Here we review these advances, placing them in the context of decades of investigation of RAF regulation. We explore the insights they provide into aberrant activation of the pathway in cancer and RASopathies (developmental syndromes caused by germline mutations in components of the pathway).</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":null,"pages":null},"PeriodicalIF":12.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Life of Translocations. 易位的一生。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2024-08-01 Epub Date: 2024-07-02 DOI: 10.1146/annurev-biochem-030122-040444
Tom A Rapoport
{"title":"A Life of Translocations.","authors":"Tom A Rapoport","doi":"10.1146/annurev-biochem-030122-040444","DOIUrl":"10.1146/annurev-biochem-030122-040444","url":null,"abstract":"<p><p>Writing a career retrospective for this prestigious series is a huge challenge. Is my story really of that much interest? One thing that is different about my life in science is the heavy influence of the turmoil of the past century. Born in the US, raised in East Germany, and returning to the US relatively late in life, I experienced research under both suboptimal and privileged conditions. My scientific story, like the political winds that blew me from one continent to the next, involved shifts into different fields. For advice to young scientists, I would suggest: Don't be afraid to start something new, it pays to be persistent, and science is a passion. In addition to telling my own story, this article also provides the opportunity to express my gratitude to my trainees and colleagues and to convey my conviction that we have the best job on earth.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":null,"pages":null},"PeriodicalIF":12.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138457328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Eukaryotic Ribosome Assembly. 真核核糖体组装。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2024-08-01 Epub Date: 2024-07-02 DOI: 10.1146/annurev-biochem-030222-113611
Arnaud Vanden Broeck, Sebastian Klinge
{"title":"Eukaryotic Ribosome Assembly.","authors":"Arnaud Vanden Broeck, Sebastian Klinge","doi":"10.1146/annurev-biochem-030222-113611","DOIUrl":"10.1146/annurev-biochem-030222-113611","url":null,"abstract":"<p><p>During the last ten years, developments in cryo-electron microscopy have transformed our understanding of eukaryotic ribosome assembly. As a result, the field has advanced from a list of the vast array of ribosome assembly factors toward an emerging molecular movie in which individual frames are represented by structures of stable ribosome assembly intermediates with complementary biochemical and genetic data. In this review, we discuss the mechanisms driving the assembly of yeast and human small and large ribosomal subunits. A particular emphasis is placed on the most recent findings that illustrate key concepts of ribosome assembly, such as folding of preribosomal RNA, the enforced chronology of assembly, enzyme-mediated irreversible transitions, and proofreading of preribosomal particles.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":null,"pages":null},"PeriodicalIF":12.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lipid Quality Control and Ferroptosis: From Concept to Mechanism. 脂质控制与铁下垂:从概念到机制。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2024-08-01 Epub Date: 2024-07-02 DOI: 10.1146/annurev-biochem-052521-033527
Zhipeng Li, Mike Lange, Scott J Dixon, James A Olzmann
{"title":"Lipid Quality Control and Ferroptosis: From Concept to Mechanism.","authors":"Zhipeng Li, Mike Lange, Scott J Dixon, James A Olzmann","doi":"10.1146/annurev-biochem-052521-033527","DOIUrl":"10.1146/annurev-biochem-052521-033527","url":null,"abstract":"<p><p>Cellular quality control systems sense and mediate homeostatic responses to prevent the buildup of aberrant macromolecules, which arise from errors during biosynthesis, damage by environmental insults, or imbalances in enzymatic and metabolic activity. Lipids are structurally diverse macromolecules that have many important cellular functions, ranging from structural roles in membranes to functions as signaling and energy-storage molecules. As with other macromolecules, lipids can be damaged (e.g., oxidized), and cells require quality control systems to ensure that nonfunctional and potentially toxic lipids do not accumulate. Ferroptosis is a form of cell death that results from the failure of lipid quality control and the consequent accumulation of oxidatively damaged phospholipids. In this review, we describe a framework for lipid quality control, using ferroptosis as an illustrative example to highlight concepts related to lipid damage, membrane remodeling, and suppression or detoxification of lipid damage via preemptive and damage-repair lipid quality control pathways.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":null,"pages":null},"PeriodicalIF":12.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107590052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Racial Stress, Racial Trauma, and Evidence-Based Strategies for Coping and Empowerment. 种族压力、种族创伤和以证据为基础的应对和赋权策略。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2024-07-01 Epub Date: 2024-07-02 DOI: 10.1146/annurev-clinpsy-081122-020235
Samantha C Holmes, Manzar Zare, Angela M Haeny, Monnica T Williams
{"title":"Racial Stress, Racial Trauma, and Evidence-Based Strategies for Coping and Empowerment.","authors":"Samantha C Holmes, Manzar Zare, Angela M Haeny, Monnica T Williams","doi":"10.1146/annurev-clinpsy-081122-020235","DOIUrl":"10.1146/annurev-clinpsy-081122-020235","url":null,"abstract":"<p><p>Racial stress and racial trauma refer to psychological, physiological, and behavioral responses to race-based threats and discriminatory experiences. This article reviews the evidence base regarding techniques for coping with racial stress and trauma. These techniques include self-care, self-compassion, social support, mindfulness, cognitive restructuring, cognitive defusion, identity-affirming practices and development of racial/ethnic identity, expressive writing, social action and activism, and psychedelics. These strategies have shown the potential to mitigate psychological symptoms and foster a sense of empowerment among individuals affected by racial stress and trauma. While the ultimate goal should undoubtedly be to address the root cause of racism, it is imperative to acknowledge that until then, implementing these strategies can effectively provide much-needed support for individuals affected by racism.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":null,"pages":null},"PeriodicalIF":12.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Acute Alcohol Consumption on Sexuality: A Look at Psychological Mechanisms. 急性饮酒对性行为的影响：心理机制研究
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2024-07-01 Epub Date: 2024-07-02 DOI: 10.1146/annurev-clinpsy-080921-075423
William H George, Jessica A Blayney, Kelly Cue Davis
{"title":"Impact of Acute Alcohol Consumption on Sexuality: A Look at Psychological Mechanisms.","authors":"William H George, Jessica A Blayney, Kelly Cue Davis","doi":"10.1146/annurev-clinpsy-080921-075423","DOIUrl":"10.1146/annurev-clinpsy-080921-075423","url":null,"abstract":"<p><p>Alcohol's link with sexuality is long-standing and prominent. While research continues to document robust associations between drinking and sexual behavior, scientific attention now centers primarily on evaluating mechanisms and attendant theoretical frameworks to advance our understanding of how alcohol exerts a causal impact. We describe four domains with reliable evidence of alcohol effects: sexualized social perceptions, sexual arousal, sexual risk taking, and sexual assault. We consider three contextual frames: distal factors associated with encountering opportunities for alcohol-involved sex, proximal factors associated with alcohol's acute effects, and distal-proximal interactions. We then examine the empirical support for mechanisms embedded within four theoretical frameworks: alcohol disinhibition, alcohol expectancy, alcohol myopia, and emotion regulation. Support for disinhibition mechanisms is evident with sexual arousal only. Expectancy and myopia mechanisms enjoy support across domains and make up bases for integrative expectancy-myopia causal explanations. Emotion regulation mechanisms evidence preliminary support in risk taking and sexual assault. Implications and future directions are considered.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":null,"pages":null},"PeriodicalIF":12.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Scientific Basis for the Regulation of Flavors in Tobacco Products. 烟草制品中香料监管的科学依据》。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2024-07-01 Epub Date: 2024-07-02 DOI: 10.1146/annurev-clinpsy-080921-075624
Krysten W Bold, Grace Kong, Stephanie S O'Malley
{"title":"The Scientific Basis for the Regulation of Flavors in Tobacco Products.","authors":"Krysten W Bold, Grace Kong, Stephanie S O'Malley","doi":"10.1146/annurev-clinpsy-080921-075624","DOIUrl":"10.1146/annurev-clinpsy-080921-075624","url":null,"abstract":"<p><p>Effective tobacco policies are important for reducing the harm of tobacco use and can have a broad impact at the population level. This review provides an overview of how clinical science can inform tobacco policies with a focus on policies related to flavored tobacco products, using menthol cigarettes as an illustrative example. Specifically, this review summarizes the role of flavors in tobacco use and the history of regulation of flavored tobacco products by the US Food and Drug Administration (FDA), provides an overview of clinical research methods used to contribute to the scientific evidence to inform FDA tobacco policies, discusses key findings related to menthol tobacco products using these methods, and proposes future directions for clinical research. As the tobacco marketplace continues to evolve with new products and flavor chemicals, ongoing clinical science will be essential for establishing evidence-based policies to protect public health and reduce tobacco-related health disparities.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":null,"pages":null},"PeriodicalIF":12.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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