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Cellular Contributions to Glymphatic and Lymphatic Waste Clearance in the Brain 细胞对大脑淋巴管和淋巴管废物清除的贡献
IF 7.2 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2024-08-12 DOI: 10.1101/cshperspect.a041370
Leon C.D. Smyth, Natalie Beschorner, Maiken Nedergaard, Jonathan Kipnis
{"title":"Cellular Contributions to Glymphatic and Lymphatic Waste Clearance in the Brain","authors":"Leon C.D. Smyth, Natalie Beschorner, Maiken Nedergaard, Jonathan Kipnis","doi":"10.1101/cshperspect.a041370","DOIUrl":"https://doi.org/10.1101/cshperspect.a041370","url":null,"abstract":"Cerebrospinal fluid (CSF) bathes and cushions the brain; however, it also serves a major role in the clearance of metabolic wastes and in the distribution of glucose, lipids, and amino acids. Unlike every other organ in the body, the brain parenchyma lacks a traditional lymphatic system to drain fluids and central nervous system (CNS) antigens. It was historically assumed that all brain wastes were removed by endogenous processing, such as phagocytosis and autophagy, while excess fluids drained directly into the blood. However, the twin discoveries of the glial-lymphatic (glymphatic) system and meningeal lymphatics have transformed our understanding of brain waste clearance. The glymphatic system describes the movement of fluids through the subarachnoid space (SAS), the influx along periarterial spaces into the brain parenchyma, and the ultimate efflux back into the SAS along perivenous spaces where it comes into direct contact with the meningeal lymphatics. The dura mater of the meninges contains a bona fide lymphatic network that can drain CSF that has entered the dura. Together, these pathways provide insights into the clearance of molecules and fluids from the brain, and show that the CNS is physically connected to the adaptive immune system. Here, we outline the glymphatic and lymphatic systems, and describe the cellular components that are important to their function.","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"32 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Diversity of Skeletal Muscle Fiber Types 骨骼肌纤维类型的多样性
IF 7.2 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2024-08-12 DOI: 10.1101/cshperspect.a041477
Stefano Schiaffino, Francesco Chemello, Carlo Reggiani
{"title":"The Diversity of Skeletal Muscle Fiber Types","authors":"Stefano Schiaffino, Francesco Chemello, Carlo Reggiani","doi":"10.1101/cshperspect.a041477","DOIUrl":"https://doi.org/10.1101/cshperspect.a041477","url":null,"abstract":"The widespread presence of slow-red and fast-white muscles in all vertebrates supports the evolutionary advantage of having two types of motors available for animal movement—a slow economical motor used for most activities, and a fast energetically costly motor used for rapid movements and emergency actions, and actions that require a lot of force. Skeletal muscles are composed of multiple fiber types whose structural and functional properties have only in part been characterized. Further progress in this field is mainly occurring along two directions: Multiomics approaches are providing a global picture of the molecular composition of muscle fibers up to the single fiber and single nucleus level. Signaling studies are identifying many transcription factors and pathways controlling fiber-type specification. These new data should now be integrated into a wider whole-body context by defining the matching between muscle fiber and motor neuron heterogeneity in the neuromuscular system, as well as the relevance of muscle fiber types in systemic homeostatic functions, including metabolism and thermogenesis.","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"74 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Glial Origins of Inherited White Matter Disorders 遗传性白质疾病的神经胶质起源
IF 7.2 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2024-08-12 DOI: 10.1101/cshperspect.a041457
Anjana Sevagamoorthy, Adeline Vanderver, Jamie L. Fraser, Jennifer Orthmann-Murphy
{"title":"Glial Origins of Inherited White Matter Disorders","authors":"Anjana Sevagamoorthy, Adeline Vanderver, Jamie L. Fraser, Jennifer Orthmann-Murphy","doi":"10.1101/cshperspect.a041457","DOIUrl":"https://doi.org/10.1101/cshperspect.a041457","url":null,"abstract":"Inherited white matter disorders (IWMDs) are a phenotypically and genotypically heterogeneous group of disorders affecting the central nervous system (CNS) with or without peripheral neuropathy. They are classified either as leukodystrophies (LDs), with primary glial abnormalities, or genetic leukoencephalopathies (gLEs), where other CNS cells are involved. As a group, these disorders are common, with an incidence of 1 in 7500 births. However, IWMDs often go undiagnosed or suffer delayed or misdiagnosis due to their heterogeneous presentation. Many of these disorders present with lethal secondary manifestations that can be prevented through early disease recognition, periodic surveillance, and preventative management. Emerging therapeutics, including gene therapy trials for metachromatic leukodystrophy (MLD) and adrenoleukodystrophy (ALD), suggest disease progression may be slowed or even prevented if treated early. Therapies for IWMDs that target glial cells or the peripheral immune system may provide novel insights for treating acquired disorders of white matter.","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"40 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Autophagy in Skeletal Muscle 骨骼肌中的自噬作用
IF 7.2 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2024-08-12 DOI: 10.1101/cshperspect.a041565
Anais Franco-Romero, Marco Sandri, Stefano Schiaffino
{"title":"Autophagy in Skeletal Muscle","authors":"Anais Franco-Romero, Marco Sandri, Stefano Schiaffino","doi":"10.1101/cshperspect.a041565","DOIUrl":"https://doi.org/10.1101/cshperspect.a041565","url":null,"abstract":"Skeletal muscle fibers possess, like all cells of our body, an evolutionary conserved autophagy machinery, which allows them to segregate unfolded proteins and damaged organelles within autophagosomes, and to induce fusion of autophagosomes with lysosomes, leading to degradation of those altered cell constituents. This process may be selective for specific cell components, as in the case of glycogen (glycophagy) or organelles, as with mitochondria (mitophagy). The autophagic flux is activated by fasting, and contributes with the proteasome to provide the organism with amino acids required for survival. Autophagy is also essential for the normal turnover of muscle proteins and organelles, as shown by the degenerative changes induced by genetic block of the autophagic mechanism, and in several myopathies. Autophagy is enhanced in muscle by exercise and impaired during aging, suggesting that aging-dependent muscle dysfunction could be delayed by boosting autophagy.","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"1 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Myotendinous Junction—Form and Function 肌腱接头--形态与功能
IF 7.2 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2024-08-12 DOI: 10.1101/cshperspect.a041500
Abigail L. Mackey
{"title":"The Myotendinous Junction—Form and Function","authors":"Abigail L. Mackey","doi":"10.1101/cshperspect.a041500","DOIUrl":"https://doi.org/10.1101/cshperspect.a041500","url":null,"abstract":"A critical link in the chain of force transmission from muscle fiber cross-bridge to bone is the interface between muscle and tendon—the myotendinous junction (MTJ). To meet the challenge of connecting these two tissues, the MTJ is specialized molecularly and morphologically. Distinct transcriptional profiles are evident for the myonuclei at the myofiber tips and a population of mononuclear tendon cells at the MTJ, demonstrating support from both sides in MTJ maintenance. Paradoxically, despite this high degree of specialization, the MTJ remains susceptible to strain (rupture) injury and is often associated with failed tissue healing. Incomplete understanding of the nature of the MTJ and the elements contributing to its plasticity hinder tackling this unsolved clinical challenge. The goal of this review is to summarize key structural and molecular features of the MTJ, discuss MTJ adaptation in response to mechanical (un)loading, aging, and injury, and highlight the major unanswered questions surrounding the MTJ.","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"56 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Nodes of Ranvier: Mechanisms of Assembly and Maintenance 兰维耶结节：组装和维护机制
IF 7.2 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2024-08-12 DOI: 10.1101/cshperspect.a041361
Matthew N. Rasband, Elior Peles
{"title":"The Nodes of Ranvier: Mechanisms of Assembly and Maintenance","authors":"Matthew N. Rasband, Elior Peles","doi":"10.1101/cshperspect.a041361","DOIUrl":"https://doi.org/10.1101/cshperspect.a041361","url":null,"abstract":"Action potential propagation along myelinated axons requires clustered voltage-gated sodium and potassium channels. These channels must be restricted to nodes of Ranvier where the action potential is regenerated. Several mechanisms have evolved to facilitate and ensure the correct assembly and stabilization of these essential axonal domains. This review highlights the current understanding of the axon-intrinsic and glial-extrinsic mechanisms that control the formation and maintenance of the nodes of Ranvier in both the peripheral (PNS) and central (CNS) nervous systems.","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"55 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Astrocyte Regulation of Synapse Formation, Maturation, and Elimination. 星形胶质细胞对突触形成、成熟和消除的调控作用
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2024-08-01 DOI: 10.1101/cshperspect.a041352
Won-Suk Chung, Katherine T Baldwin, Nicola J Allen
{"title":"Astrocyte Regulation of Synapse Formation, Maturation, and Elimination.","authors":"Won-Suk Chung, Katherine T Baldwin, Nicola J Allen","doi":"10.1101/cshperspect.a041352","DOIUrl":"10.1101/cshperspect.a041352","url":null,"abstract":"<p><p>Astrocytes play an integral role in the development, maturation, and refinement of neuronal circuits. Astrocytes secrete proteins and lipids that instruct the formation of new synapses and induce the maturation of existing synapses. Through contact-mediated signaling, astrocytes can regulate the formation and state of synapses within their domain. Through phagocytosis, astrocytes participate in the elimination of excess synaptic connections. In this work, we will review key findings on the molecular mechanisms of astrocyte-synapse interaction with a focus on astrocyte-secreted factors, contact-mediated mechanisms, and synapse elimination. We will discuss this in the context of typical brain development and maintenance, as well as consider the consequences of dysfunction in these pathways in neurological disorders, highlighting a role for astrocytes in health and disease.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
The Biology of Lipids. 脂质生物学
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2024-08-01 DOI: 10.1101/cshperspect.a041713
Robert G Parton, Kai Simons
{"title":"The Biology of Lipids.","authors":"Robert G Parton, Kai Simons","doi":"10.1101/cshperspect.a041713","DOIUrl":"10.1101/cshperspect.a041713","url":null,"abstract":"<p><p>Lipids are the defining features of cellular membranes. They act collectively to form a variety of different structures, and understanding their complex behavior represents an early example of systems biology. A multidisciplinary approach is needed to analyse the functions of lipids in biological systems, and new work is providing fascinating insights into their roles in membrane biology, metabolism, signaling, subcellular dynamics and various disease processes.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Overcoming Obstacles to Gene-Edited Solutions to Climate Challenges. 克服基因编辑气候挑战解决方案的障碍。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2024-08-01 DOI: 10.1101/cshperspect.a041677
L Val Giddings
{"title":"Overcoming Obstacles to Gene-Edited Solutions to Climate Challenges.","authors":"L Val Giddings","doi":"10.1101/cshperspect.a041677","DOIUrl":"10.1101/cshperspect.a041677","url":null,"abstract":"<p><p>Gene editing and genetic modification hold enormous potential to deliver solutions to multiple climate change challenges. The most important rate-limiting obstacles impeding their development and deployment are not technical, but rather counterproductive policies and regulations. These are driven in part by the mistaken apprehension of widespread public opposition. These obstacles are described and solutions to overcoming them are presented.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Endoplasmic Reticulum Membrane Homeostasis and the Unfolded Protein Response. 内质网膜稳态和折叠蛋白反应
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2024-08-01 DOI: 10.1101/cshperspect.a041400
Robert Ernst, Mike F Renne, Aamna Jain, Alexander von der Malsburg
{"title":"Endoplasmic Reticulum Membrane Homeostasis and the Unfolded Protein Response.","authors":"Robert Ernst, Mike F Renne, Aamna Jain, Alexander von der Malsburg","doi":"10.1101/cshperspect.a041400","DOIUrl":"10.1101/cshperspect.a041400","url":null,"abstract":"<p><p>The endoplasmic reticulum (ER) is the key organelle for membrane biogenesis. Most lipids are synthesized in the ER, and most membrane proteins are first inserted into the ER membrane before they are transported to their target organelle. The composition and properties of the ER membrane must be carefully controlled to provide a suitable environment for the insertion and folding of membrane proteins. The unfolded protein response (UPR) is a powerful signaling pathway that balances protein and lipid production in the ER. Here, we summarize our current knowledge of how aberrant compositions of the ER membrane, referred to as lipid bilayer stress, trigger the UPR.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139520198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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