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Golgi fragmentation - One of the earliest organelle phenotypes in Alzheimer's disease neurons.

التفاصيل البيبلوغرافية
العنوان: Golgi fragmentation - One of the earliest organelle phenotypes in Alzheimer's disease neurons.
المؤلفون: Haukedal H; Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark., Corsi GI; Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.; Center for Non-coding RNA in Technology and Health, University of Copenhagen, Frederiksberg, Denmark., Gadekar VP; Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.; Center for Non-coding RNA in Technology and Health, University of Copenhagen, Frederiksberg, Denmark., Doncheva NT; Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.; Center for Non-coding RNA in Technology and Health, University of Copenhagen, Frederiksberg, Denmark.; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark., Kedia S; Centre for Neuroscience, Indian Institute of Science, Bengaluru, India., de Haan N; Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Chandrasekaran A; Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark., Jensen P; Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark., Schiønning P; Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark., Vallin S; Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark., Marlet FR; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Poon A; Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark., Pires C; Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark., Agha FK; Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Wandall HH; Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Cirera S; Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark., Simonsen AH; Danish Dementia Research Centre, Department of Neurology, Neuroscience Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Nielsen TT; Danish Dementia Research Centre, Department of Neurology, Neuroscience Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Nielsen JE; Danish Dementia Research Centre, Department of Neurology, Neuroscience Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Hyttel P; Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark., Muddashetty R; Institute for Stem Cell Science and Regenerative Medicine, Bengaluru, India., Aldana BI; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Gorodkin J; Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.; Center for Non-coding RNA in Technology and Health, University of Copenhagen, Frederiksberg, Denmark., Nair D; Centre for Neuroscience, Indian Institute of Science, Bengaluru, India., Meyer M; Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.; Department of Neurology, Odense University Hospital, Odense, Denmark., Larsen MR; Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark., Freude K; Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
المصدر: Frontiers in neuroscience [Front Neurosci] 2023 Feb 16; Vol. 17, pp. 1120086. Date of Electronic Publication: 2023 Feb 16 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101478481 Publication Model: eCollection Cited Medium: Print ISSN: 1662-4548 (Print) Linking ISSN: 1662453X NLM ISO Abbreviation: Front Neurosci Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Lausanne : Frontiers Research Foundation
مستخلص: Alzheimer's disease (AD) is the most common cause of dementia, with no current cure. Consequently, alternative approaches focusing on early pathological events in specific neuronal populations, besides targeting the well-studied amyloid beta (Aβ) accumulations and Tau tangles, are needed. In this study, we have investigated disease phenotypes specific to glutamatergic forebrain neurons and mapped the timeline of their occurrence, by implementing familial and sporadic human induced pluripotent stem cell models as well as the 5xFAD mouse model. We recapitulated characteristic late AD phenotypes, such as increased Aβ secretion and Tau hyperphosphorylation, as well as previously well documented mitochondrial and synaptic deficits. Intriguingly, we identified Golgi fragmentation as one of the earliest AD phenotypes, indicating potential impairments in protein processing and post-translational modifications. Computational analysis of RNA sequencing data revealed differentially expressed genes involved in glycosylation and glycan patterns, whilst total glycan profiling revealed minor glycosylation differences. This indicates general robustness of glycosylation besides the observed fragmented morphology. Importantly, we identified that genetic variants in Sortilin-related receptor 1 ( SORL1 ) associated with AD could aggravate the Golgi fragmentation and subsequent glycosylation changes. In summary, we identified Golgi fragmentation as one of the earliest disease phenotypes in AD neurons in various in vivo and in vitro complementary disease models, which can be exacerbated via additional risk variants in SORL1 .
Competing Interests: HW owns stocks and is a consultant for and co-founder of EbuMab ApS, Hemab ApS, and GO- Therapeutics, Inc., all not involved in, or related to, the research performed in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Haukedal, Corsi, Gadekar, Doncheva, Kedia, de Haan, Chandrasekaran, Jensen, Schiønning, Vallin, Marlet, Poon, Pires, Agha, Wandall, Cirera, Simonsen, Nielsen, Nielsen, Hyttel, Muddashetty, Aldana, Gorodkin, Nair, Meyer, Larsen and Freude.)
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فهرسة مساهمة: Keywords: Alzheimer’s disease; Golgi fragmentation; disease modelling; hiPSC; neurons
تواريخ الأحداث: Date Created: 20230306 Latest Revision: 20230307
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9978754
DOI: 10.3389/fnins.2023.1120086
PMID: 36875643
قاعدة البيانات: MEDLINE
الوصف
تدمد:1662-4548
DOI:10.3389/fnins.2023.1120086