{"doi":"10.3389/fcell.2023.1359465","title":"Editorial: Cytoskeletal alterations in aging and disease","abstract":"The cytoskeleton of eukaryotic cells consists of microtubules, actin and intermediate filaments, which are highly interconnected and compartmentalized in polarized cells, such as neurons (Iwanski and Kapitein, 2023;Kevenaar and Hoogenraad, 2015;Leterrier et al., 2017). In particular, these filaments are much more than just pure structural elements and ensure various additional functions critical for neuronal development and maintenance (Iwanski and Kapitein, 2023;Dent and Baas, 2014;Coles and Bradke, 2015;Yuan et al., 2017). Not surprisingly, dysfunction of any of these components can cause neurodegenerative diseases, such as Alzheimer's, Charcot-Marie-Tooth disease (CMT) or Hereditary spastic Paraplegia (HSP) (Martnez-Hernandez et al., 2022;Morris et al., 2023;Bomont et al. 2023;Costa and Sousa, 2023;Matamoros and Baas, 2016).Microtubules, which are rod-like, polarized structures assembled from alpha/beta-tubulin dimers form the basis for organelle transport and modulate cell shape and behavior (Conde and Caceres, 2009;Guedes-Dias and Holzbaur, 2019). Interestingly, microtubules can be highly heterogeneous across cellular and subcellular compartments due to several factors: 1) cell-type specific expression of tubulin genes; 2) locally active enzymes catalyzing posttranslational modifications (PTMs); and 3) various flavors of Microtubule-Associated Proteins (MAPs) (Janke and Bulinski, 2011;Roll-Mecak, 2020;McKenna et al., 2023). However, how these different factors assemble and segregate in developing and mature neurons to drive specialized microtubule functions remains elusive (Chakraborti et al., 2016;Bodakuntla et al., 2021;Moutin et al., 2021;Atkins et al., 2023;Pero et al., 2023).Recent innovative strategies to label or image specific microtubule subpopulations with high resolution led to novel concepts suggesting that the tubulin and MAP codes can cooperatively and locally drive microtubule lattice compaction or expansion, renewal, and rescue to tune microtubule structure and dynamics (Iwanski & Kapitein., 2023;Janke and Magiera, 2020). In addition, all cytoskeleton elements and associated proteins are heavily modified through PTMs, many of which are associated with neuronal development and degeneration. However, key which are critical in normal development, can exacerbate AD progression when misregulated, while selective tau phosphorylation, which is indicated in AD, may promote axonal growth when physiologically regulated. These intriguing results are important for understanding neuronal cytoskeleton in health, disease and aging through multiple lenses focusing on different neuronal states. However, the underlying molecular mechanisms require further studies so that we may know how to regulate these PTMs, which can be a double-edged sword for neurons. In this context, the review by Bomont et al. pointed out that the dynamicity of neurofilaments, which is based on their fine-tuned assembly/transport/degradation to sustain key structural and electrophysiological properties of the neurons, is critically influenced by PTMs (Yuan et al., 2017;Yuan and Nixon, 2023). These data shed new perspectives on the etiology and treatment of neurofilament-related neurodegenerative disorders (e.g. CMT or amyotrophic lateral sclerosis, (Rao and Nixon, 2003;Perrot and Eyer, 2009;Didonna and Opal, 2019;Laura et al., 2019;Stone et al., 2021).Importantly, neurofilaments were shown to influence microtubule dynamics in neurons (Yadav et al., 2016). Such crosstalk may be established and regulated by PTMs and MAPs, leading to finetuning of neuronal morphology, cytoarchitecture, and physiology. This proposed mechanism may provide an additional step in untangling the complexity behind the cytoskeleton-mediated regulation of neuronal homeostasis and its contribution to aging and diseases. Following this idea, determining how cytoskeleton composition and axon morphology change during aging would be very informative (Kounakis and Tavernarakis, 2019;K","journal":"Frontiers in Cell and Developmental Biology","year":2024,"id":489570,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1334868,"name":"Coralie Fassier","orcid":"0000-0003-3015-4281","position":1,"is_corresponding":false},{"id":1090567,"name":"Yuyu Song","orcid":"0000-0002-9196-1610","position":2,"is_corresponding":false},{"id":1334867,"name":"Monika S. Brill","orcid":"0000-0001-5422-9175","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T02:08:28.548530Z","pmid":"38299006","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}