Philosophical transactions of the Royal Society of London. Series B, Biological sciences最新文献_第2页

Multi-predator feeding aggregations: understanding dynamic communities through functional niches and demographic analysis tools. 多捕食者捕食聚集：通过功能生态位和人口统计分析工具了解动态群落。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-15 DOI: 10.1098/rstb.2025.0198

Wednesday Davis, Rochelle Constantine, Gaia Dell'Ariccia

{"title":"Multi-predator feeding aggregations: understanding dynamic communities through functional niches and demographic analysis tools.","authors":"Wednesday Davis, Rochelle Constantine, Gaia Dell'Ariccia","doi":"10.1098/rstb.2025.0198","DOIUrl":"10.1098/rstb.2025.0198","url":null,"abstract":"Multi-predator feeding aggregations (MPFAs) are ocean events whereby two or more species forage on the same or co-occurring prey. Such communities are dynamic, with community structure reflecting the connections between species and the benefits and costs of associations. The analysis of MPFAs provides an overview of ecosystem health, with social networks reflecting prey and available resources. Demographic analyses of MPFAs can act as process-based indicators of community responses to rapid change. To understand complex community dynamics, we identified community types in MPFAs using hierarchical clustering and determined the social associations and roles of the different species present. We collected data on 179 MPFA events, recording 55.4 hours of behavioural observations from 33 843 individuals belonging to 19 seabird and three cetacean species in the Hauraki Gulf, New Zealand. Eight MPFA community types were identified, representing planktivorous, scavenger or polytrophic aggregations. Seabird-cetacean and seabird-seabird associations dominated species associations. We interpret the species' roles by combining our observations of behavioural states with knowledge from the literature. The study of marine MPFAs offers a community-level perspective for understanding community dynamics and food-web organization under future ecosystem changes. Using social network analyses, we advance the understanding of species interconnectedness to better inform ecosystem-based conservation management. This article is part of the theme issue 'Multi-predator feeding aggregations in the pelagic waters'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1961","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interactions between multi-species marine predator aggregations and the energy landscape. 多物种海洋捕食者聚集与能源景观之间的相互作用。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-15 DOI: 10.1098/rstb.2025.0195

Yannis P Papastamatiou, Johann Mourier, Gil Iosilevskii

{"title":"Interactions between multi-species marine predator aggregations and the energy landscape.","authors":"Yannis P Papastamatiou, Johann Mourier, Gil Iosilevskii","doi":"10.1098/rstb.2025.0195","DOIUrl":"10.1098/rstb.2025.0195","url":null,"abstract":"Multi-species predator aggregations can be found in both coastal and pelagic ecosystems, forming for both foraging and refuging (resting) purposes. The energy landscape represents the power costs required to move through or reside within a habitat. As species may differ in their morphology, buoyancy and length, there may be species-specific heterogeneity in their energy landscapes. Here, we highlight how the energy landscape may influence the small-scale distribution of predators within an aggregation and potentially their ability to forage. We focus on negatively buoyant predators, such as sharks, which can reduce their metabolic costs by swimming in upwelling currents. We develop a biomechanical model to show how shark length and buoyancy alter the energetic benefit sharks obtain from swimming in upwelling currents. We provide evidence of small-scale spatial separation between shark species within a French Polynesian channel, which may be related to species exploiting optimal energetic environments. Second, we show how the energy landscape influences patch residence times in foraging predators and how this may differ between species. For instance, different species within a multi-species foraging aggregation may quit the patch at different prey densities. Overall, the energy landscape may help to drive the distribution of species within aggregations or even inter-species patterns of assortativity. This article is part of the theme issue 'Multi-predator feeding aggregations in the pelagic'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1961","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How volant seabirds benefit from sub-surface predators during multi-predator feeding aggregations. 在多捕食者的觅食聚集中，狂暴的海鸟如何从地下捕食者中获益。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-15 DOI: 10.1098/rstb.2025.0199

Max Licht, Edna Correia, Martin Wikelski, Jens Krause

{"title":"How volant seabirds benefit from sub-surface predators during multi-predator feeding aggregations.","authors":"Max Licht, Edna Correia, Martin Wikelski, Jens Krause","doi":"10.1098/rstb.2025.0199","DOIUrl":"10.1098/rstb.2025.0199","url":null,"abstract":"Multi-predator feeding aggregations are common in marine ecosystems and frequently involve seabirds. Often labelled opportunistic 'scroungers', volant seabirds derive diverse benefits from the association with sub-surface predators (such as cetaceans, pinnipeds, Teleosts) which can significantly enhance their hunting performance. In this opinion piece, we outline the major mechanisms through which sub-surface predators benefit volant seabirds, based on recent quantitative evidence and hypotheses that warrant further research. The mechanisms we identified are: herding prey to the surface, prey detection (local enhancement), reduction of prey cohesion, access to immobilized prey and the attentional overload of prey. Furthermore, we discuss potential interactions between these mechanisms and mechanism-based predictions which can be tested in the field. We propose that the associations with sub-surface predators are ecologically relevant to the extent that they may influence selection breeding sites. We conclude by discussing methodological advancements that have the possibility to further research in this field and go over open questions they might help to answer in the future. This article is part of the theme issue 'Multi-predator feeding aggregations in the pelagic waters'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1961","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Disruption of RNA metabolism and its impact on protein homeostasis. RNA代谢的破坏及其对蛋白质稳态的影响。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0267

Susana M D A Garcia

{"title":"Disruption of RNA metabolism and its impact on protein homeostasis.","authors":"Susana M D A Garcia","doi":"10.1098/rstb.2025.0267","DOIUrl":"https://doi.org/10.1098/rstb.2025.0267","url":null,"abstract":"Repeat-associated disorders arise from expansions of nucleotide repeats in coding or non-coding regions, producing RNAs that accumulate and disrupt cellular homeostasis through mechanisms collectively termed RNA repeat toxicity. This process complements proteotoxicity in coding-region expansions and is increasingly recognized as a major contributor to pathogenesis. Expanded repeat RNAs form stable secondary structures that sequester RNA-binding proteins (RBPs), such as Muscleblind-like, alter splicing and activate small RNA pathways, broadly impacting gene expression. Myotonic dystrophy type 1 (DM1) exemplifies RNA-mediated toxicity, with expanded CUG repeats in the DMPK 3' untranslated region driving nuclear foci formation, RBP sequestration and transcriptome-wide changes. Beyond RNA processing defects, DM1 exhibits systemic dysfunction, notably affecting energy metabolism and mitochondrial function, which recent evidence suggests may be disrupted early and progressively during disease development. These metabolic changes intersect with proteostasis failure, amplifying cellular stress and contributing to systemic pathology. A deeper understanding of the molecular networks that drive metabolic and mitochondrial dysfunction, and their role in proteostasis collapse, will be critical for elucidating disease onset and progression. This knowledge will enable the identification of novel therapeutic targets and biomarkers, offering strategies that go beyond RNA-centric approaches to restore cellular homeostasis in repeat-based disorders. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1960","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

More than the 'master regulator of cytosolic proteostasis': new roles for HSF1 in promoting tissue health. 不仅仅是“细胞质蛋白静止的主要调节因子”：HSF1在促进组织健康中的新作用。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0270

John Labbadia

{"title":"More than the 'master regulator of cytosolic proteostasis': new roles for HSF1 in promoting tissue health.","authors":"John Labbadia","doi":"10.1098/rstb.2025.0270","DOIUrl":"https://doi.org/10.1098/rstb.2025.0270","url":null,"abstract":"Maintaining protein homeostasis (proteostasis) is crucial for long-term tissue health. This requires the action of stress response pathways and protein quality control mechanisms that act within or across different sub-cellular compartments to preserve proteome integrity. Within the cytosol/nucleus, the loss of proteostasis induces a transcriptional programme known as the heat-shock response (HSR) through activation of heat-shock factor 1 (HSF1). The HSR rapidly elevates levels of molecular chaperones, co-chaperones and protein degradation factors that restore proteostasis in the cytosol/nucleus. As a result, the ability of HSF1 to promote tissue health has long been attributed to its capacity to safeguard the cytosolic/nucleosolic proteome. However, over the past 15 years, it has become apparent that HSF1 activity is also intimately coupled with the biogenesis and maintenance of other organelles, including mitochondria, peroxisomes, the endoplasmic reticulum, lysosomes and chloroplasts. This suggests that HSF1 promotes tissue health in plants and animals through mechanisms beyond the maintenance of cytosolic/nucleosolic proteostasis. In this opinion piece, I will discuss advances in our understanding of the interplay between HSF1 and organelle homeostasis and make the case that the existing model for the relationship between HSF1 and tissue health should be expanded to encompass these additional roles. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1960","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Traumatic brain injury induces cell-type-specific remodelling of the proteostasis network. 外伤性脑损伤诱导蛋白质静止网络的细胞类型特异性重构。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0264

Jonathan Lefkowitz, Milo Taylor, Aditya Kumar, Ruchira M Jha, Dhivyaa Rajasundaram, Prajwal Ciryam

{"title":"Traumatic brain injury induces cell-type-specific remodelling of the proteostasis network.","authors":"Jonathan Lefkowitz, Milo Taylor, Aditya Kumar, Ruchira M Jha, Dhivyaa Rajasundaram, Prajwal Ciryam","doi":"10.1098/rstb.2025.0264","DOIUrl":"https://doi.org/10.1098/rstb.2025.0264","url":null,"abstract":"Traumatic brain injury (TBI) triggers competing damage and repair processes that can result in chronic neurodegenerative protein conformational disorders. Acute alterations in proteostasis have been reported after injury, but a comprehensive understanding of changes to the proteostasis network (PN) has been limited by the complex cellular pathology of TBI. The recent enumeration of the human PN and advances in single-cell transcriptomics make it possible to delineate PN dynamics in multifactorial diseases such as TBI. Here, we leverage archival mouse and human transcriptomic data to identify cell-type-specific Sub-PNs in the brain and their alteration by TBI. We find characteristic PN gene expression profiles in many cell types and subtypes, reflecting tremendous diversity in the enrichment of specific PN processes. TBI induces a broad transcriptional remodelling of translation, the ubiquitin-proteasome system and nuclear proteostasis machinery across cell types. In addition to this shared response, numerous cell-type-specific responses occur, some of which are conserved between mouse and human, despite differences in injury mechanism and timing. Our extensive characterization of the PN transcriptome across cell type and disease reveals potentially modifiable mechanisms of PN alteration in TBI. More broadly, our results provide a framework for elucidating changes to the PN in complex diseases. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1960","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From aggregate structure to disease trajectory: the role of the proteostasis network. 从聚集结构到疾病轨迹：蛋白质平衡网络的作用。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0276

Jessica Tittelmeier, Carmen Nussbaum-Krammer

{"title":"From aggregate structure to disease trajectory: the role of the proteostasis network.","authors":"Jessica Tittelmeier, Carmen Nussbaum-Krammer","doi":"10.1098/rstb.2025.0276","DOIUrl":"https://doi.org/10.1098/rstb.2025.0276","url":null,"abstract":"Neurodegenerative diseases are characterized by the accumulation of a small number of misfolded proteins, yet they differ markedly in cellular vulnerability and clinical outcome. We propose that this heterogeneity arises from the interaction between two largely orthogonal variables: the structural identities of protein aggregates and the identities of the cellular proteostasis networks (PNs) that engage them. Protein aggregates exist as structurally diverse assemblies with distinct intrinsic properties. At the same time, PNs vary between cell types, disease states and ageing in their composition, capacity and plasticity. As a result, the same aggregate can be efficiently cleared in one cellular context but persist, be remodelled, or give rise to self-propagating species in another. Likewise, the same PN can be protective or harmful, depending on the aggregate it encounters. Because neither aggregates nor PNs are static, their interaction evolves over time, leading to dynamic feedback between aggregate identity and PN state that shapes disease onset, progression and clinical symptoms. This view reframes neurodegenerative disease as a failure of compatibility between specific aggregate structures and the cellular protein quality control network that processes them rather than as a uniform collapse of proteostasis, and provides a framework for understanding selective vulnerability and disease trajectories. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1960","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Disulphide maintenance systems and proteostasis. 二硫化物维护系统和蛋白质平衡。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0280

James D West

{"title":"Disulphide maintenance systems and proteostasis.","authors":"James D West","doi":"10.1098/rstb.2025.0280","DOIUrl":"https://doi.org/10.1098/rstb.2025.0280","url":null,"abstract":"Protein disulphide formation between cysteine residues impacts protein folding and function, yet the context in which it occurs often determines whether it is beneficial or detrimental. To ensure proper disulphide status, organisms have evolved compartment-specific disulphide maintenance systems. Some of these, like the thioredoxin and glutaredoxin systems, promote disulphide reduction in oxidized substrates, whereas others, like the protein disulphide isomerase, Mia40 and Dsb systems, primarily oversee proper structural disulphide formation within client proteins. Here, I review how these disulphide maintenance systems operate and explore how they fit within the proteostasis network. Each system functions in helping proteins achieve and/or retain their functional states. Along these lines, thioredoxins can prevent aggregation of some proteins and, working with holdases, regulate recovery from protein misfolding during oxidative stress. Separately, protein disulphide isomerases work collaboratively with core molecular chaperones (e.g. Hsp70 family members) to aid in protein folding, enabling the correct formation of structural disulphides in clients. In addition, some disulphide maintenance enzymes influence protein degradation of improperly folded proteins by the proteasome. This review highlights several key ways that protein disulphide maintenance and proteostasis go hand-in-hand. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1960","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteostasis and ageing dissidence. 蛋白质停滞和衰老异议。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0266

Neethu Babu, Katie Whalen, Brian Freeman

{"title":"Proteostasis and ageing dissidence.","authors":"Neethu Babu, Katie Whalen, Brian Freeman","doi":"10.1098/rstb.2025.0266","DOIUrl":"https://doi.org/10.1098/rstb.2025.0266","url":null,"abstract":"Proteostasis, the process governing the dynamic regulation of protein synthesis, folding and degradation, is critical for maintaining cell function and organismal health. Ageing disrupts this intricate system, leading to inactive, misfolded and/or aggregated proteins that contribute to age-associated pathologies. Here, we explore current findings on proteostasis and its deterioration during ageing with an attention to three major pathways: molecular chaperone (MC), ubiquitin-proteasome system (UPS) and autophagy-lysosomal pathway. Components in all three paths undergo age-dependent decline in both expression and function, with each impairment having select initial outcomes on the health of a proteome. For example, loss in the MC path may cause nascent chain defects, whereas a decline in the UPS may result in the accumulation of toxic aggregates. Notably, the interconnectedness of these pathways results in reciprocal reactions in all three. Understanding how each path connects to the others and how these connections are regulated offers promising strategies to restore proteome integrity and extend a healthy lifespan. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1960","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cellular and systemic modifiers of alpha-synuclein proteostasis. -突触核蛋白蛋白静止的细胞和系统调节剂。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-10-01 DOI: 10.1098/rstb.2025.0275

Suzanne Couzijn, Anna P Ainslie, Alejandro Herron-Bedoya, Ellen A A Nollen

{"title":"Cellular and systemic modifiers of alpha-synuclein proteostasis.","authors":"Suzanne Couzijn, Anna P Ainslie, Alejandro Herron-Bedoya, Ellen A A Nollen","doi":"10.1098/rstb.2025.0275","DOIUrl":"https://doi.org/10.1098/rstb.2025.0275","url":null,"abstract":"Ageing is a primary risk factor for neurodegenerative disorders, including Parkinson's disease (PD). As individuals age, their cells become less efficient in maintaining protein homeostasis, leading to an increased likelihood of protein misfolding and aggregation. A hallmark of PD and other synucleinopathies is the accumulation of alpha-synuclein protein aggregates in affected neurons, a process that is exacerbated by ageing. While cellular mechanisms that regulate protein aggregation have been a primary focus of research, recent studies suggest that other, systemic age-related mechanisms may contribute to alpha-synuclein toxicity. Understanding these alternative pathways is crucial for the development of effective therapeutic strategies to combat neurodegenerative diseases, such as PD. In this review, we synthesize current insights into the biological mechanisms underlying alpha-synuclein toxicity at the organismal level. We highlight key open questions and discuss how these findings may inform the development of targeted interventions to prevent or delay age-related synucleinopathies. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1960","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0