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Book: Polyglutamine disorders

Nóbrega, Clévio / Pereira de Almeida, Luís

(Advances in experimental medicine and biology ; 1049)

2018

Author's details	Clévio Nóbrega, Luís Pereira de Almeida editors
Series title	Advances in experimental medicine and biology ; 1049
Collection
Language	English
Size	VIII, 469 Seiten, Illustrationen
Publisher	Springer
Publishing place	Cham
Publishing country	Switzerland
Document type	Book
HBZ-ID	HT019615957
ISBN	978-3-319-71778-4 ; 9783319717791 ; 3-319-71778-2 ; 3319717790
Database	Catalogue ZB MED Medicine, Health

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Book ; Online ; E-Book: Polyglutamine disorders

Nóbrega, Clévio / Pereira de Almeida, Luís

(Advances in experimental medicine and biology ; 1049)

2018

Author's details	Clévio Nóbrega, Luís Pereira de Almeida editors
Series title	Advances in experimental medicine and biology ; 1049
Collection
Keywords	Medicine ; Medical genetics ; Neurosciences ; Neurology
Subject code	612.8
Language	English
Size	1 Online-Ressource (viii, 469 Seiten), Illustrationen
Publisher	Springer
Publishing place	Cham
Publishing country	Switzerland
Document type	Book ; Online ; E-Book
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
HBZ-ID	HT019629424
ISBN	978-3-319-71779-1 ; 9783319717784 ; 3-319-71779-0 ; 3319717782
DOI	10.1007/978-3-319-71779-1
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Neuropeptide Y (NPY) intranasal delivery alleviates Machado-Joseph disease.

Duarte-Neves, Joana / Cavadas, Cláudia / Pereira de Almeida, Luís

Scientific reports

2021 Volume 11, Issue 1, Page(s) 3345

Abstract: Machado-Joseph disease (MJD) is the most common dominantly-inherited ataxia worldwide with no effective treatment to prevent, stop or alleviate its progression. Neuropeptide Y (NPY) is a neuroprotective agent widely expressed in the mammalian brain. Our ... ...

Abstract	Machado-Joseph disease (MJD) is the most common dominantly-inherited ataxia worldwide with no effective treatment to prevent, stop or alleviate its progression. Neuropeptide Y (NPY) is a neuroprotective agent widely expressed in the mammalian brain. Our previous work showed that NPY overexpression mediated by stereotaxically-injected viral vectors mitigates motor deficits and neuropathology in MJD mouse models. To pursue a less invasive translational approach, we investigated whether intranasal administration of NPY would alleviate cerebellar neuropathology and motor and balance impairments in a severe MJD transgenic mouse model. For that, a NPY solution was administered into mice nostrils 5 days a week. Upon 8 weeks of treatment, we observed a mitigation of motor and balance impairments through the analysis of mice behavioral tests (rotarod, beam walking, pole and swimming tests). This was in line with a reduction of cerebellar pathology, evidenced by a preservation of cerebellar granular layer and of Purkinje cells and reduction of mutant ataxin-3 aggregate numbers. Furthermore, intranasal administration of NPY did not alter body weight gain, food intake, amount of body fat nor cholesterol or triglycerides levels. Our findings support the translational potential of intranasal infusion of NPY as a pharmacological intervention in MJD.
MeSH term(s)	Administration, Intranasal ; Animals ; Ataxin-3/genetics ; Ataxin-3/metabolism ; Cerebellum/metabolism ; Cerebellum/pathology ; Disease Models, Animal ; Machado-Joseph Disease/drug therapy ; Machado-Joseph Disease/genetics ; Machado-Joseph Disease/metabolism ; Machado-Joseph Disease/pathology ; Mice ; Mice, Transgenic ; Neuropeptide Y/pharmacology ; Purkinje Cells/metabolism ; Purkinje Cells/pathology
Chemical Substances	Neuropeptide Y ; Ataxin-3 (EC 3.4.19.12) ; Atxn3 protein, mouse (EC 3.4.19.12)
Language	English
Publishing date	2021-02-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-82339-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Extracellular Vesicles Physiological Role and the Particular Case of Disease-Spreading Mechanisms in Polyglutamine Diseases.

Moreira, Ricardo / Mendonça, Liliana S / Pereira de Almeida, Luís

International journal of molecular sciences

2021 Volume 22, Issue 22

Abstract: Recent research demonstrated pathological spreading of the disease-causing proteins from one focal point across other brain regions for some neurodegenerative diseases, such as Parkinson's and Alzheimer's disease. Spreading mediated by extracellular ... ...

Abstract	Recent research demonstrated pathological spreading of the disease-causing proteins from one focal point across other brain regions for some neurodegenerative diseases, such as Parkinson's and Alzheimer's disease. Spreading mediated by extracellular vesicles is one of the proposed disease-spreading mechanisms. Extracellular vesicles are cell membrane-derived vesicles, used by cells for cell-to-cell communication and excretion of toxic components. Importantly, extracellular vesicles carrying pathological molecules, when internalized by "healthy" cells, may trigger pathological pathways and, consequently, promote disease spreading to neighboring cells. Polyglutamine diseases are a group of genetic neurodegenerative disorders characterized by the accumulation of mutant misfolded proteins carrying an expanded tract of glutamines, including Huntington's and Machado-Joseph disease. The pathological spread of the misfolded proteins or the corresponding mutant mRNA has been explored. The understanding of the disease-spreading mechanism that plays a key role in the pathology progression of these diseases can result in the development of effective therapeutic approaches to stop disease progression, arresting the spread of the toxic components and disease aggravation. Therefore, the present review's main focus is the disease-spreading mechanisms with emphasis on polyglutamine diseases and the putative role played by extracellular vesicles in this process.
MeSH term(s)	Animals ; Extracellular Vesicles/genetics ; Extracellular Vesicles/metabolism ; Humans ; Huntington Disease/genetics ; Huntington Disease/metabolism ; Machado-Joseph Disease/genetics ; Machado-Joseph Disease/metabolism ; Peptides/genetics ; Peptides/metabolism
Chemical Substances	Peptides ; polyglutamine (26700-71-0)
Language	English
Publishing date	2021-11-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222212288
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: RNA-based liposomes for oral cancer: From biophysical characterization to biological evaluation.

Lopes-Nunes, Jéssica / Simões, Pedro / Moreira, David / Leandro, Kevin / Nobre, Rui Jorge / Pereira de Almeida, Luís / Campello, Maria Paula Cabral / Oliveira, Maria Cristina / Paulo, António / Coutinho, Ana / Melo, Ana M / Tomaz, Cândida / Cruz, Carla

International journal of biological macromolecules

2024 Volume 259, Issue Pt 2, Page(s) 129157

Abstract: Oral cancer incidence and mortality are increasing over time. The most common therapies for oral cancers are surgery and radiotherapy, either used alone or combined, and immunotherapy can be also an option. Although there are several therapeutic options, ...

Abstract	Oral cancer incidence and mortality are increasing over time. The most common therapies for oral cancers are surgery and radiotherapy, either used alone or combined, and immunotherapy can be also an option. Although there are several therapeutic options, none of them are completely effective, and in addition, there are numerous associated side effects. To overcome these limitations, researchers have been trying to reduce these drawbacks by using drug delivery systems that carry drugs for specific delivery to cancer cells. For that purpose, RNA-coated liposomes to selectively deliver the ligands C
MeSH term(s)	Humans ; Liposomes/chemistry ; Drug Delivery Systems ; Cell Line ; Mouth Neoplasms/drug therapy ; Dexamethasone/pharmacology
Chemical Substances	Liposomes ; Dexamethasone (7S5I7G3JQL)
Language	English
Publishing date	2024-01-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2023.129157
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Article ; Online: Viral-based animal models in polyglutamine disorders.

Henriques, Carina / Lopes, Miguel M / Silva, Ana C / Lobo, Diana D / Badin, Romina Aron / Hantraye, Philippe / Pereira de Almeida, Luís / Nobre, Rui Jorge

Brain : a journal of neurology

2024 Volume 147, Issue 4, Page(s) 1166–1189

Abstract: Polyglutamine disorders are a complex group of incurable neurodegenerative disorders caused by an abnormal expansion in the trinucleotide cytosine-adenine-guanine tract of the affected gene. To better understand these disorders, our dependence on animal ... ...

Abstract	Polyglutamine disorders are a complex group of incurable neurodegenerative disorders caused by an abnormal expansion in the trinucleotide cytosine-adenine-guanine tract of the affected gene. To better understand these disorders, our dependence on animal models persists, primarily relying on transgenic models. In an effort to complement and deepen our knowledge, researchers have also developed animal models of polyglutamine disorders employing viral vectors. Viral vectors have been extensively used to deliver genes to the brain, not only for therapeutic purposes but also for the development of animal models, given their remarkable flexibility. In a time- and cost-effective manner, it is possible to use different transgenes, at varying doses, in diverse targeted tissues, at different ages, and in different species, to recreate polyglutamine pathology. This paper aims to showcase the utility of viral vectors in disease modelling, share essential considerations for developing animal models with viral vectors, and provide a comprehensive review of existing viral-based animal models for polyglutamine disorders.
MeSH term(s)	Animals ; Trinucleotide Repeat Expansion ; Peptides/genetics ; Disease Models, Animal ; Transgenes
Chemical Substances	polyglutamine (26700-71-0) ; Peptides
Language	English
Publishing date	2024-02-13
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awae012
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Article ; Online: A new protocol for whole-brain biodistribution analysis of AAVs by tissue clearing, light-sheet microscopy and semi-automated spatial quantification.

Lopes, Miguel M / Paysan, Jacques / Rino, José / Lopes, Sara M / Pereira de Almeida, Luís / Cortes, Luísa / Nobre, Rui Jorge

Gene therapy

2022

Abstract: Recombinant adeno-associated virus (rAAV) has become one of the most promising gene delivery systems for both in vitro and in vivo applications. However, a key challenge is the lack of suitable imaging technologies to evaluate delivery, biodistribution ... ...

Abstract	Recombinant adeno-associated virus (rAAV) has become one of the most promising gene delivery systems for both in vitro and in vivo applications. However, a key challenge is the lack of suitable imaging technologies to evaluate delivery, biodistribution and tropism of rAAVs and efficiently monitor disease amelioration promoted by AAV-based therapies at a whole-organ level with single-cell resolution. Therefore, we aimed to establish a new pipeline for the biodistribution analysis of natural and new variants of AAVs at a whole-brain level by tissue clearing and light-sheet fluorescence microscopy (LSFM). To test this platform, neonatal C57BL/6 mice were intravenously injected with rAAV9 encoding EGFP and, after sacrifice, brains were processed by standard immunohistochemistry and a recently released aqueous-based clearing procedure. This clearing technique required no dedicated equipment and rendered highly cleared brains, while simultaneously preserving endogenous fluorescence. Moreover, three-dimensional imaging by LSFM allowed the quantitative analysis of EGFP at a whole-brain level, as well as the reconstruction of Purkinje cells for the retrieval of valuable morphological information inaccessible by standard immunohistochemistry. In conclusion, the pipeline herein described takes the AAVs to a new level when coupled to LSFM, proving its worth as a bioimaging tool in tropism and gene therapy studies.
Language	English
Publishing date	2022-11-01
Publishing country	England
Document type	Journal Article
ZDB-ID	1191036-7
ISSN	1476-5462 ; 0969-7128
ISSN (online)	1476-5462
ISSN	0969-7128
DOI	10.1038/s41434-022-00372-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Using genetically modified extracellular vesicles as a non-invasive strategy to evaluate brain-specific cargo

Rufino-Ramos, David / Lule, Sevda / Mahjoum, Shadi / Ughetto, Stefano / Cristopher Bragg, D. / Pereira de Almeida, Luís / Breakefield, Xandra O. / Breyne, Koen

Biomaterials. 2022 Feb., v. 281

2022

Abstract: The lack of techniques to trace brain cell behavior in vivo hampers the ability to monitor status of cells in a living brain. Extracellular vesicles (EVs), nanosized membrane-surrounded vesicles, released by virtually all brain cells might be able to ... ...

Abstract	The lack of techniques to trace brain cell behavior in vivo hampers the ability to monitor status of cells in a living brain. Extracellular vesicles (EVs), nanosized membrane-surrounded vesicles, released by virtually all brain cells might be able to report their status in easily accessible biofluids, such as blood. EVs communicate among tissues using lipids, saccharides, proteins, and nucleic acid cargo that reflect the state and composition of their source cells. Currently, identifying the origin of brain-derived EVs has been challenging, as they consist of a rare population diluted in an overwhelming number of blood and peripheral tissue-derived EVs. Here, we developed a sensitive platform to select out pre-labelled brain-derived EVs in blood as a platform to study the molecular fingerprints of brain cells. This proof-of-principle study used a transducible construct tagging tetraspanin (TSN) CD63, a membrane-spanning hallmark of EVs equipped with affinity, bioluminescent, and fluorescent tags to increase detection sensitivity and robustness in capture of EVs secreted from pre-labelled cells into biofluids. Our platform enables unprecedented efficient isolation of neural EVs from the blood. These EVs derived from pre-labelled mouse brain cells or engrafted human neuronal progenitor cells (hNPCs) were submitted to multiplex analyses, including transcript and protein levels, in compliance with the multibiomolecule EV carriers. Overall, our novel strategy to track brain-derived EVs in a complex biofluid opens up new avenues to study EVs released from pre-labelled cells in near and distal compartments into the biofluid source.
Keywords	biocompatible materials ; bioluminescence ; blood ; brain ; compliance ; detection limit ; fluorescence ; humans ; mice ; neurons
Language	English
Dates of publication	2022-02
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2022.121366
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Extracellular communication between brain cells through functional transfer of Cre mRNA mediated by extracellular vesicles.

Rufino-Ramos, David / Leandro, Kevin / Perdigão, Pedro R L / O'Brien, Killian / Pinto, Maria Manuel / Santana, Magda M / van Solinge, Thomas S / Mahjoum, Shadi / Breakefield, Xandra O / Breyne, Koen / Pereira de Almeida, Luís

Molecular therapy : the journal of the American Society of Gene Therapy

2023 Volume 31, Issue 7, Page(s) 2220–2239

Abstract: In the central nervous system (CNS), the crosstalk between neural cells is mediated by extracellular mechanisms, including brain-derived extracellular vesicles (bdEVs). To study endogenous communication across the brain and periphery, we explored Cre- ... ...

Abstract	In the central nervous system (CNS), the crosstalk between neural cells is mediated by extracellular mechanisms, including brain-derived extracellular vesicles (bdEVs). To study endogenous communication across the brain and periphery, we explored Cre-mediated DNA recombination to permanently record the functional uptake of bdEVs cargo over time. To elucidate functional cargo transfer within the brain at physiological levels, we promoted the continuous secretion of physiological levels of neural bdEVs containing Cre mRNA from a localized region in the brain by in situ lentiviral transduction of the striatum of Flox-tdTomato Ai9 mice reporter of Cre activity. Our approach efficiently detected in vivo transfer of functional events mediated by physiological levels of endogenous bdEVs throughout the brain. Remarkably, a spatial gradient of persistent tdTomato expression was observed along the whole brain, exhibiting an increment of more than 10-fold over 4 months. Moreover, bdEVs containing Cre mRNA were detected in the bloodstream and extracted from brain tissue to further confirm their functional delivery of Cre mRNA in a novel and highly sensitive Nanoluc reporter system. Overall, we report a sensitive method to track bdEV transfer at physiological levels, which will shed light on the role of bdEVs in neural communication within the brain and beyond.
MeSH term(s)	Mice ; Animals ; Mice, Transgenic ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Integrases/genetics ; Integrases/metabolism ; Brain/metabolism ; Extracellular Vesicles/metabolism
Chemical Substances	Cre recombinase (EC 2.7.7.-) ; RNA, Messenger ; Integrases (EC 2.7.7.-)
Language	English
Publishing date	2023-05-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2023.05.012
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Article ; Online: In Vitro

Pereira, Patrícia / Neto, Ana S / Rodrigues, Ana S / Barros, Inês / Miranda, Catarina / Ramalho-Santos, João / Pereira de Almeida, Luís / Ferreira, José M F / Coelho, Jorge F J / Fonseca, Ana C

Polymers

2023 Volume 15, Issue 10

Abstract: This study investigates the osteogenic differentiation of umbilical-cord-derived human mesenchymal stromal cells (hUC-MSCs) on biphasic calcium phosphate (BCP) scaffolds derived from cuttlefish bone doped with metal ions and coated with polymers. First, ... ...

Abstract	This study investigates the osteogenic differentiation of umbilical-cord-derived human mesenchymal stromal cells (hUC-MSCs) on biphasic calcium phosphate (BCP) scaffolds derived from cuttlefish bone doped with metal ions and coated with polymers. First, the
Language	English
Publishing date	2023-05-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527146-5
ISSN	2073-4360 ; 2073-4360
ISSN (online)	2073-4360
ISSN	2073-4360
DOI	10.3390/polym15102256
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