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Transcriptomic Profiling of Human Pluripotent Stem Cell-Derived Cerebellar Organoids

Transcriptomic Profiling of Human Pluripotent Stem Cell-Derived Cerebellar Organoids | iBB | Scoop.it

 

Endogenous human brain tissue is not easily available for studying neurodevelopment and neurodegenerative diseases. However, human pluripotent stem cells (PSCs) have been used to generate a variety of glial and neuronal cells of the central nervous system. Still, reproducible protocols for generating in vitro models of the human cerebellum are scarce. In this context, Silva et al. describe the scalable production of human PSC-derived cerebellar organoids using single-use vertical-wheel bioreactors. The transcriptomic profile of cerebellar organoids derived under dynamic conditions demonstrates a faster cerebellar differentiation combined with significant enrichment of extracellular matrix and upregulation of transcripts involved in angiogenesis when compared with the static protocol. The authors anticipate that large-scale production of cerebellar organoids may help developing models for drug screening, toxicological tests and studying pathological pathways involved in cerebellar degeneration.

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Luís Martins to Defend PhD Thesis in Biotechnology and Biosciences

Luís Martins to Defend PhD Thesis in Biotechnology and Biosciences | iBB | Scoop.it

Luís Miguel Candeias Martins will be defending his PhD thesis in Biotechnology and Biosciences at Instituto Superior Técnico, Tuesday the 18th of May 2021, at 14:00 (https://videoconf-colibri.zoom.us/j/82200706553). During the last years, and under the supervision of Prof. Isabel Sá-Correia from BSRG-iBB, Luís studied the genetic tolerance determinants for multiple stresses in S. cerevisiae and the potential of oleaginous red yeasts for the efficient carbon substrates conversion present in pectin-rich hydrolysates. The title of his thesis is “Valorisation of pectin-rich agro-industrial residues by yeasts: Potential and Challenges”.

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Modeling Rett Syndrome with Human Pluripotent Stem Cells: Mechanistic Outcomes and Future Clinical Perspectives

Modeling Rett Syndrome with Human Pluripotent Stem Cells: Mechanistic Outcomes and Future Clinical Perspectives | iBB | Scoop.it

Rett syndrome (RTT) is a rare neurodevelopmental disorder caused by mutations in the gene encoding for the MeCP2 protein. Among different roles, MeCP2 has a high phenotypic impact during the different stages of brain development. Thus, it is essential to investigate the function of MeCP2 and its regulated targets. In a review paper published in the International Journal of Molecular Sciences, a team of researchers at SCERG-iBB provides a brief summary of the main neurological features of RTT and of the impact of MeCP2 mutations in the neuropathophysiology of the disease. A thorough revision of recent advances and future prospects of RTT modeling using human neural cells derived from pluripotent stem cells and its contribution for the current and future clinical trials for RTT is also provided.

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Transcriptomic Profiling of Human Pluripotent Stem Cell-Derived Cerebellar Organoids

Transcriptomic Profiling of Human Pluripotent Stem Cell-Derived Cerebellar Organoids | iBB | Scoop.it

 

Endogenous human brain tissue is not easily available for studying neurodevelopment and neurodegenerative diseases. However, human pluripotent stem cells (PSCs) have been used to generate a variety of glial and neuronal cells of the central nervous system. Still, reproducible protocols for generating in vitro models of the human cerebellum are scarce. In this context, Silva et al. describe the scalable production of human PSC-derived cerebellar organoids using single-use vertical-wheel bioreactors. The transcriptomic profile of cerebellar organoids derived under dynamic conditions demonstrates a faster cerebellar differentiation combined with significant enrichment of extracellular matrix and upregulation of transcripts involved in angiogenesis when compared with the static protocol. The authors anticipate that large-scale production of cerebellar organoids may help developing models for drug screening, toxicological tests and studying pathological pathways involved in cerebellar degeneration.

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Burkholderia cenocepacia BCAM2418-induced Antibody Inhibits Bacterial Adhesion

Burkholderia cenocepacia BCAM2418-induced Antibody Inhibits Bacterial Adhesion | iBB | Scoop.it

B. cenocepacia is a contact-dependent bacterium known for its capacity of causing respiratory infections. Among a panel of adhesins used by B. cenocepacia to contact with host cells, trimeric autotransporter adhesins (TAAs) are of particular interest. In a recent paper published in Cellular Microbiology, a BSRG-iBB team (Andreia Pimenta, Nuno Bernardes, Dalila Mil-Homens and Arsénio M Fialho) together with Michelle Kilcoyne and Lokesh Joshi from the National University of Ireland Galway, Galway, Ireland, were able to uncover the roles of the TAA BCAM2418, as an adhesin and the type of host glycans that serve as recognition targets. This work reveals the importance of BCAM2418 as a mediator of early host-bacteria crosstalk.

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Amin Javidanbardan Wins the Eppendorf Poster Award at the 6th BioProScale Symposium

Amin Javidanbardan Wins the Eppendorf Poster Award at the 6th BioProScale Symposium | iBB | Scoop.it

Amin Javidanbardan won the Eppendorf Poster Award at the 6th BioProScale Symposium “Innovative scale-up and scale-down for bioprocess intensification.” The event took place virtually from 29.03. to 31.03.2021. Amin presented his poster with the title “Rapid and cost-effective fabrication of microchromatography integrated with microelectrode impedance sensor.” Amin, a Marie Curie Early-Stage Researcher of the ITN action “CODOBIO,” is enrolled in the Ph.D. program of Biotechnology and Biosciences and is being supervised by Ana Azevedo (iBB-BERG) and João Pedro Conde (INESC-MN), both from the Department of Bioengineering. Congratulations Amin!

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LEGOlizing Synthetic Pathways to Enable Microbial Production of Levulinic Acid

LEGOlizing Synthetic Pathways to Enable Microbial Production of Levulinic Acid | iBB | Scoop.it

Levulinic acid is a versatile platform molecule with potential to be used in replacement of oil-derived catalysts explored by the chemical industry for the synthesis of many add-value products. Unlike other carboxylic acids of interest whose microbial production has been addressed, levulinic acid is not described to be produced by living systems which restrains its microbial production. Exploring the power of synthetic biology in settling new-to-nature pathways (through the association between metabolites and/or enzymes that are not found in nature), hundreds of potential combinations were screened exploring different metabolic retrobiosynthesis tools followed by extensive manual curation and genome scale metabolic modeling. Five complete synthetic pathways (with identified intermediates and enzymes) were identified as promising candidates to enable microbial production of levulinic acid. The results of this study, resulting from a collaboration between the iBB team led by Nuno P Mira and the team of Kristala Prather from MIT, were recently published in ACS Synthetic Biology. Not only does the herein described approach offer a platform for future implementation of microbial production of levulinic acid, but it also provides an organized research strategy that can be used as a framework for the implementation of other new-to-nature biosynthetic pathways for the production of add-value chemicals, thus fostering the emerging field of synthetic industrial microbiotechnology. 

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New CoLAB to Foster Translation and Drug Discovery

New CoLAB to Foster Translation and Drug Discovery | iBB | Scoop.it

FCT has just approved a new Collaborative Laboratory to foster translation and drug discovery - BioScale. BioScale wants to fill the gap existing between biomedical research and pharmaceutical industry in the transformation of scientific results into new drug products. The vision of the CoLAB is to capitalize on existing innovative research at academia by developing new biological targets and platforms for generating new drug candidates ready to be invested by industries. iBB is one of the co-partners of BioScale, which further includes iMM (the proponent), Universidade de Coimbra, Biocant, Roche Farmacêutica Quimica, Magnify Afterburner Capital Partners, VerticalSentinel, TargTex, LiMM Therapeutics, CellmAbs and BSIM Therapeutics.

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mRNA Vaccine Manufacturing: Challenges and Bottlenecks

mRNA Vaccine Manufacturing: Challenges and Bottlenecks | iBB | Scoop.it

Vaccines are one of the most important tools in public health and play an important role in infectious diseases control. mRNA vaccines are reaching the stoplight as a new alternative to conventional vaccines due to their precision, safe profile and flexible manufacturing. In fact, the first Covid-19 vaccines to receive regulatory approval are based on mRNA technology. In a joint review just published in Vaccine, Sara Sousa Rosa, Miguel Prazeres, Ana Azevedo from BERG-iBB, together with Marco Marques from University College London, describe the current state-of-art of mRNA vaccines, focusing on the challenges and bottlenecks of manufacturing that need to be addressed to turn this new vaccination technology into an effective, fast and cost-effective response to emerging health crises.

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Exploring Oleaginous Red Yeasts for Sugar Beet Pulp Valorization

Exploring Oleaginous Red Yeasts for Sugar Beet Pulp Valorization | iBB | Scoop.it

Agro-industrial residues rich in pectin are generated in high amounts worldwide from the sugar industry or the industrial processing of fruits and vegetables. A recent paper by BSRG-iBB researchers, published in the Journal of Fungi (special issue “Yeast Biorefineries” (edited by Isabel Sá-Correia and Naseem Gaur), describes the optimization of the performance of Rhodotorula strains envisaging the use of the major carbon sources present in Sugar Beet Pulp (SBP) hydrolysates. SBP valorization through the production of lipids and carotenoids by the oleaginous red yeasts examined, supported by complete catabolism of the major carbon sources present, looks promising for industrial implementation. The work was conducted by the PhD student of the IST PhD Programme in Biotechnology and Biosciences Luís C. Martins (FCT_DP AEM programme fellowship) under the supervision of Isabel Sá-Correia. This work was developed in the context of the ERA-NET-Industrial Biotechnology-2 project, “YEASTPEC-Engineering of the yeast Saccharomyces cerevisiae for bioconversion of pectin-containing agro-industrial side-streams”.

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Burkholderia cenocepacia Transcriptome During the Early Contacts with Giant Plasma Membrane Vesicles

Burkholderia cenocepacia Transcriptome During the Early Contacts with Giant Plasma Membrane Vesicles | iBB | Scoop.it

Burkholderia cenocepacia is a human contact-dependent pathogenic bacterium known for its capacity of causing severe opportunistic respiratory infections. B. cenocepacia uses a complex machinery for primary adherence with host cells. In a recent paper published in Scientific Reports, a BSRG-iBB team (Andreia Pimenta, Nuno Bernardes, Dalila Mil-Homens and Arsénio M Fialho) together with Marta M Alves from CQE, IST, have developed a RNASeq-based approach that led to identify adhesion candidate genes that were not previously reported in the context of a B. cenocepacia infection. This study presents a innovative technique in which their use Giant Plasma Membrane Vesicles (GPMVs) from a bronchial epithelial cell line as a cell-like alternative to investigate the steps involved in the adhesion process of B. cenocepacia.

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Detection of SARS-CoV-2 in Clinical and Environmental Samples

Detection of SARS-CoV-2 in Clinical and Environmental Samples | iBB | Scoop.it

A new research project “CAPTURA- Use of functionalized particles for the enrichment and efficient detection of SARS-CoV-2 in clinical and environmental samples” has been recently awarded to IST by the Compete 2020 programme (Call 02/SAICT/2020 - SAICT, Projetos de IC&DT, Testar com Ciência). The project’s overarching goal is to detect SARS-CoV-2 in samples other than nasopharyngeal and oropharyngeal swabs, like urine, saliva and also in environmental samples, like residual waters. Efforts will be also mobilized to develop tests for the rapid detection of SARS-CoV-2 antigens. The project is a consortium of three research units of IST - iBB, the Center for Nuclear Sciences and Technologies and the Laboratory of Analysis of IST - and is headed by Leonilde Moreira from BSRG-iBB.

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Portuguese Platform of BioImaging is Now a Euro-Bioimaging Node

Portuguese Platform of BioImaging is Now a Euro-Bioimaging Node | iBB | Scoop.it

The Portuguese Platform of BioImaging (PPBI) is now a Euro-Bioimaging Node. The Advanced Fluorescence Microscopy Facility at iBB-IST joined this application, and now also integrates the Euro-BioImaging network. Ana M. Melo (Facility Head) presented on 22nd February 2021 our site, specialized in quantitative imaging and dedicated to functional imaging and single-molecule techniques.

 

 

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Asymmetric Synthesis with a Marine Transaminase

Asymmetric Synthesis with a Marine Transaminase | iBB | Scoop.it

w-Transaminases (w-TA) have a pivotal role in the synthesis of chiral amines used as building blocks for drugs and pharmaceuticals. In a recently published paper, Carlos JC Rodrigues (iBB-BERG), Manuel Ferrer (CSIC, Spain) and Carla CCR de Carvalho (iBB-BERG) used a w-TA from a marine bacterium to synthesize the fluorine chiral amine (S)-1-(4-trifluoromethylphenyl)ethylamine from a bulky ketone. An in situ product removal (ISPR) approach using an aqueous organic two-phase system was used to mitigate product inhibition, and engineering tools were used to increase substrate mass transfer without affecting the ability of the organic phase to prevent inhibition of the enzyme activity. The insights gained during process development may be valuable for future process applications of TA reactions.

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Cláudia Alves to Defend PhD Thesis in Biotechnology and Biosciences

Cláudia Alves to Defend PhD Thesis in Biotechnology and Biosciences | iBB | Scoop.it

Cláudia Patrícia Almeida Alves will be defending her PhD thesis in Biotechnology and Biosciences at Instituto Superior Técnico, Friday the 14th of May 2021, at 14:00 am (https://videoconf-colibri.zoom.us/j/82471896554). During the last years, and under the supervision of Gabriel Monteiro and Miguel Prazeres from iBB, Cláudia engineered Escherichia coli strains for the production of minicircle vectors by resolvase-catalyzed in vivo recombination. The title of her thesis is “Escherichia coli Genome Engineering For Improved Minicircle Production". Yo can check more about Cláudia's work here.

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Minicircle‐based Expression of VEGF in Mesenchymal Stromal Cells from Human Tissues

Minicircle‐based Expression of VEGF in Mesenchymal Stromal Cells from Human Tissues | iBB | Scoop.it

Mesenchymal stromal cells (MSC) have been exploited for the treatment of ischemic diseases given their angiogenic potential. A recent study published in the Journal of Gene Medicine by BERG and SCERG researchers compares the angiogenic potential of MSC obtained from bone marrow (BM), adipose tissue (AT) and umbilical cord matrix (UCM) that were genetically modified with VEGF‐encoding minicircle vectors. Transfected cells displayed higher in vitro angiogenic potential than non‐transfected controls, as demonstrated by functional in vitro assays, but no significant differences were observed among cells from different sources.

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Manufacturing of Bacteriophages for Therapeutic Applications

Manufacturing of Bacteriophages for Therapeutic Applications | iBB | Scoop.it

The use of bacteriophages, or simply phages, as therapeutic agents offer is expected to reduce antibiotic use and mitigate the emergence of multidrug-resistant bacteria. The development of phage therapies should be accompanied by the improvement of phage biomanufacturing processes. In a review published in Biotechnology Advances, Jorge João, João Lampreia, Miguel Prazeres and Ana Azevedo from BERG-iBB showcase current processes used for the manufacturing of phages and discuss future alternatives. On the production side, key factors (e.g. bacterial physiological state, phage infection, operation parameters) are described alongside with the different bioreactor operation modes. Traditional methods used in the initial phage isolation steps are then described followed by the presentation of current state-of-the-art purification approaches. Continuous purification of phages is finally presented as a future biomanufacturing trend.

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Ana Isabel Campos to Defend PhD Thesis in Biotechnology and Biosciences

Ana Isabel de Vila-Santa Braga Campos will be defending her PhD thesis in Biotechnology and Biosciences at Instituto Superior Técnico, Friday the 16th of April 2021, at 15:00 am (https://videoconf-colibri.zoom.us/j/81314376867). During the last years, and under the supervision of Nuno Mira and Frederico Ferreira from iBB, and Kristala Prather from MIT, Ana Isabel investigated how pathways for the synthesis of levulinic and itaconic acids can be engineered in yeasts. The title of her thesis is “Synthetic biology approaches to foster yeasts as hosts for the production of carboxylic acids and their derivatives: emphasis on levulinic and itaconic acids”.

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Genome Sequencing of the Non-conventional Yeast Saccharomycodes ludwigii

Genome Sequencing of the Non-conventional Yeast Saccharomycodes ludwigii | iBB | Scoop.it

Yeasts from the Saccharomycodeacea family are common in the must wine microbiome. Some species (e.g. from the Hanseniaspora genus) play an important role by positively modulating the production of aromatic chemicals, while others (e.g.  from the Saccharomycodes genus) are detrimental due to their spoilage potential. Recently, an iBB team led by Nuno Mira, in collaboration with the team of Alexandra Mendes-Ferreira from the UTAD, described the insights gathered upon extensive analysis of the genome of a S. ludwigii strain retrieved from a contaminated must, this being the first genome described for this species. This work, published in BMC Genomics, follows a previous one published in DNA Research that described, for the first time, the genome of a Hanseniaspora guilliermondii strain and that shed light into key aspects of the physiology of Hanseniaspora species relevant in the context of wine fermentation. It is expected that the comparative genomic analyses of Saccharomycodeacea species can foster their rational utilization in the wine industry (as co-adjuvants of S. cerevisiae) to obtain differentiated stylistic wines, while also contributing for a better design of efficient preservation strategies.  

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New Metagenomic Insights Into the Octocoral Microbiome

New Metagenomic Insights Into the Octocoral Microbiome | iBB | Scoop.it

Octocorals are marine invertebrates abundant in the Portuguese coast, which host complex microbiomes. Yet the functional relationship between host health and its symbiotic consortium has still to be determined. A new study from an international team led by iBB researchers Tina Keller-Costa and Rodrigo Costa employed comparative metagenomics to uncover the functional and phylogenetic features of the microbiomes of healthy tissue from three octocoral species from the Portuguese coast. The authors also explored how the octocoral microbiome shifts to a pathobiome state in one of the coral species. The study reveals that the octocoral microbiome is distinct from those of the environmental surroundings (that is, seawater and sediments), is host genus (but not species) specific, and undergoes complex structural changes in the transition to the dysbiotic state. Host-symbiont recognition, abiotic-stress response, micronutrient acquisition, and an antiviral defence arsenal comprising multiple restriction endonucleases, CRISPR/Cas systems, and phage lysogenization regulators are signatures of prokaryotic communities in octocorals. The authors argue that these features collectively contribute to the stabilization of host-microbe symbiosis in octocorals and constitute beneficial traits that can guide future studies on coral reef conservation and microbiome therapy. The article was published in the journal Microbiome.

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Special Issue “Yeast Biorefineries”

Special Issue “Yeast Biorefineries” | iBB | Scoop.it

The Special Issue “Yeast Biorefineries” edited by Isabel Sa-Correia and Naseem A. Gaur for the Journal of Fungi intends to gather the most recent and original research and review papers on the identification, development, and exploitation of robust, metabolically promising, and genetically engineered yeast strains for advanced biorefineries. Saccharomyces cerevisiae is a major cell factory for which vast biological knowledge and genetic tools are available. However, the exploitation of non-Saccharomyces yeasts is recently gaining momentum, making this large and heterogeneous group desirable for the synthesis of a wide range of added-value products, in particular lipids/oleofuels, bioethanol, carotenoids, organic acids, and biopolymers. Papers on the identification, exploitation, and development of robust, metabolically promising, and genetically engineered conventional and non-conventional yeast strains for biorefineries are welcome. Contributions that explore functional and comparative genomics analyses for understanding the physiological genomics of yeasts and the development of bioprocesses, especially those dedicated to the valorization of bioresidues and production of added-value products are also welcome.

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Técnico's PhD Student Guide 2021

Técnico's PhD Student Guide 2021 | iBB | Scoop.it

The Post-Graduation Office of IST issued a Guide for its PhD Students. The Guide is a contribution to the integration of PhD students at Instituto Superior Técnico and provides a succinct overview of a number of topics, including Doctoral milestones and requirements, as well as information about IST's organization. You can check the guide here.

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BIOTECnico PhD Alumni Seminar: Mafalda Cavalheiro

BIOTECnico PhD Alumni Seminar: Mafalda Cavalheiro | iBB | Scoop.it

Mafalda Cavalheiro will be giving a talk entitled "Deciphering Mechanisms of Pathogenesis in Candida glabrata: in the Crossroad Between Drug Resistance and Virulence ", Tuesday the 16th of March at 16:00 h via zoom. Mafalda obtained her PhD in Biotechnology and Biosciences in 2020 and is currently working at A4F – Algae for Future, as a Junior R&D Project Manager.

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iBB and the Covid-19 Testing Program at IST

iBB and the Covid-19 Testing Program at IST | iBB | Scoop.it

In the early days of the pandemic, iBB, the Center for Nuclear Sciences and Technologies (CTN2) and the Center for Structural Chemistry (CQE) joined efforts to create a laboratory for the molecular diagnostic of SARS-CoV-2 in samples collected in several nursing homes. After running more than 4500 samples, the lab focused on the implementation of a Covid-19 Testing Program at IST. Up to now close to 6000 tests have been made to members of the IST community. The IST/iBB-CTN Covid-19 lab is certified by (Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA).

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Cellulose-Based Lateral Flow Immunoassay for the Fluorescent Detection of Troponin

Cellulose-Based Lateral Flow Immunoassay for the Fluorescent Detection of Troponin | iBB | Scoop.it

Lateral flow assays (LFA) are the dominant segment in the Point-Of-Care testing market. Analytical strips made of nitrocellulose (NC) are the heart of a LFA. However, NC is not necessarily the best matrix due to the inability to control the orientation of proteins, inconsistencies in flow rates, lot-to-lot variability, flammable nature, sensitivity to humidity, and an inherent brittleness. In a paper published in Biosensors, Miguel Prazeres from BERG-iBB with colleagues from the Indian Institute of Technology show that cellulose paper possesses the adequate characteristics to replace NC in a LFA for the quantitative, fluorescence-based detection of cardiac troponin I. It is further shown that the layering of carbon nanofibers favor the generation of more intense immunofluorescence signals. The results open up the possibility for companies to develop specialized cellulose strips for LFA. The work is funded by project CBM-X.

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Intranasal Drug Delivery for Treatment of Alzheimer’s Disease

Intranasal Drug Delivery for Treatment of Alzheimer’s Disease | iBB | Scoop.it

Alzheimer’s disease (AD) is a progressive and irreversible brain disorder that hampers memory and thinking, affects the capacity to perform daily tasks, and leads to physical and cognitive incapacitation. The conventional treatment occurs by the oral route, but it presents relevant drawbacks such as low bioavailability, fast metabolism, limited brain exposure, and undesirable side effects. The intranasal route has been proposed as an alternative to deliver drugs and improve treatment of AD.  In a paper published in Drug Delivery and Translational Research, Pedro Fonte from BERG-iBB performed an overview on the strategies for drug intranasal delivery for AD treatment. In the paper, the advantages and disadvantages of the nasal route and the delivery systems developed so far are discussed. A special focus is given to the use of permeation enhancers, the types of intranasal drug delivery devices, as well as possible toxicity concerns.

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