Targets to Search for New Pharmacological Treatment in Idiopathic Parkinson’s Disease According to the Single-Neuron Degeneration Model DOI Creative Commons
Sandro Huenchuguala, Juan Segura‐Aguilar

Biomolecules, Год журнала: 2024, Номер 14(6), С. 673 - 673

Опубликована: Июнь 8, 2024

One of the biggest problems in treatment idiopathic Parkinson’s disease is lack new drugs that slow its progression. L-Dopa remains star drug this disease, although it induces severe side effects. The failure clinical studies with depends on use preclinical models based neurotoxins do not represent what happens since they induce rapid and expansive neurodegeneration. We have recently proposed a single-neuron degeneration model for requires years to accumulate enough lost neurons onset motor symptoms. This excessive formation aminochrome during neuromelanin synthesis surpass neuroprotective action enzymes DT-diaphorase glutathione transferase M2-2, which prevent neurotoxic effects aminochrome. Although an effect, stereotaxic injection endogenous neurotoxin cannot be used generate animal. Therefore, aim review evaluate strategies pharmacologically increasing expression DT diaphorase GSTM2-2 molecules vesicular monoamine transporter 2, such as pramipexole.

Язык: Английский

Exosomes as New Generation Vehicles for Drug Delivery: Biomedical Applications and Future Perspectives DOI Creative Commons
Amarjitsing Rajput,

Akansh Varshney,

Rashi Bajaj

и другие.

Molecules, Год журнала: 2022, Номер 27(21), С. 7289 - 7289

Опубликована: Окт. 27, 2022

Currently, particular interest among the scientific community is focused on exploring use of exosomes for several pharmaceutical and biomedical applications. This due to identification role as an excellent intercellular communicator by delivering requisite cargo comprising functional proteins, metabolites nucleic acids. Exosomes are smallest extracellular vesicles (EV) with sizes ranging from 30–100 nm derived endosomes. have similar surface morphology cells act a signal transduction channel between cells. They encompass different biomolecules, such acids lipids, thus rendering them naturally attractive drug delivery vehicle. Like other advanced systems, polymeric nanoparticles liposomes encapsulate substances, also gained much attention in enhancing therapeutic activity. present many advantages, compatibility living tissues, low toxicity, extended blood circulation, capability pass contents one cell another, non-immunogenic special targeting various cells, making carrier. Exosome-based molecules still early stages research clinical trials. The problems transition issues related exosome-based drugs need be overcome using tools better understanding systemic evaluation exosomes. In this current review, we summarize most up-to-date knowledge about complex biological journey biogenesis secretion, isolation techniques, characterization, loading methods, applications, challenges future perspectives

Язык: Английский

Процитировано

97

Opportunities and challenges of alpha-synuclein as a potential biomarker for Parkinson’s disease and other synucleinopathies DOI Creative Commons
Pedro Magalhães, Hilal A. Lashuel

npj Parkinson s Disease, Год журнала: 2022, Номер 8(1)

Опубликована: Июль 22, 2022

Abstract Parkinson’s disease (PD), the second most common progressive neurodegenerative disease, develops and progresses for 10–15 years before clinical diagnostic symptoms of are manifested. Furthermore, several aspects PD pathology overlap with other diseases (NDDs) linked to alpha-synuclein (aSyn) aggregation, also called synucleinopathies. Therefore, there is an urgent need discover validate early prognostic markers that reflect pathophysiology, progression, severity, potential differences in mechanisms between NDDs. The close association aSyn development synucleinopathies, along identification species biological fluids, has led increasing interest as biomarkers diagnosis differentiate it from In this review, we (1) provide overview progress toward mapping distribution brain, peripheral tissues, fluids; (2) present comparative critical analysis previous studies measured total well such modified aggregated forms different (3) highlight conceptual technical gaps challenges could hinder validation reliable biomarkers; (4) outline a series recommendations address these challenges. Finally, propose combined biomarker approach based on integrating biochemical, aggregation structure features aSyn, addition neurodegeneration. We believe capturing diversity essential develop robust assays diagnostics detection, patient stratification, monitoring differentiation This transform trial design implementation, accelerate new therapies, improve decisions treatment strategies.

Язык: Английский

Процитировано

92

Extracellular vesicles: Emerging tools as therapeutic agent carriers DOI Creative Commons
Shan Liu,

Xue Wu,

Sutapa Chandra

и другие.

Acta Pharmaceutica Sinica B, Год журнала: 2022, Номер 12(10), С. 3822 - 3842

Опубликована: Май 11, 2022

Extracellular vesicles (EVs) are secreted by both eukaryotes and prokaryotes, present in all biological fluids of vertebrates, where they transfer DNA, RNA, proteins, lipids, metabolites from donor to recipient cells cell-to-cell communication. Some EV components can also indicate the type status their parent serve as diagnostic targets for liquid biopsy. EVs natively carry or be modified contain therapeutic agents (e.g., nucleic acids, polysaccharides, small molecules) physical, chemical, bioengineering strategies. Due excellent biocompatibility stability, ideal nanocarriers bioactive ingredients induce signal transduction, immunoregulation, other effects, which targeted specific cell types. Herein, we review classification, intercellular communication, isolation, characterization strategies apply therapeutics. This focuses on recent advances applications carriers vitro research towards vivo animal models early clinical applications, using representative examples fields cancer chemotherapeutic drug, vaccine, infectious disease vaccines, regenerative medicine gene therapy. Finally, discuss current challenges therapeutics future development.

Язык: Английский

Процитировано

85

Recent progresses in exosome-based systems for targeted drug delivery to the brain DOI
Santosh Bashyal,

Thapa Chhitij,

Sang Kil Lee

и другие.

Journal of Controlled Release, Год журнала: 2022, Номер 348, С. 723 - 744

Опубликована: Июнь 23, 2022

Язык: Английский

Процитировано

82

Cell–cell communication: new insights and clinical implications DOI Creative Commons

Jimeng Su,

Ying Song,

Zhipeng Zhu

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 7, 2024

Multicellular organisms are composed of diverse cell types that must coordinate their behaviors through communication. Cell-cell communication (CCC) is essential for growth, development, differentiation, tissue and organ formation, maintenance, physiological regulation. Cells communicate direct contact or at a distance using ligand-receptor interactions. So cellular encompasses two processes: signal conduction generation intercellular transmission signals, transduction reception procession signals. Deciphering networks critical understanding metabolism. First, we comprehensively review the historical milestones in CCC studies, followed by detailed description mechanisms molecule importance main signaling pathways they mediate maintaining biological functions. Then systematically introduce series human diseases caused abnormalities progress clinical applications. Finally, summarize various methods monitoring interactions, including imaging, proximity-based chemical labeling, mechanical force analysis, downstream analysis strategies, single-cell technologies. These aim to illustrate how functions depend on these interactions complexity regulatory regulate crucial processes, homeostasis, immune responses diseases. In addition, this enhances our processes occur after cell-cell binding, highlighting its application discovering new therapeutic targets biomarkers related precision medicine. This collective provides foundation developing targeted drugs personalized treatments.

Язык: Английский

Процитировано

37

Exosomes: a review of biologic function, diagnostic and targeted therapy applications, and clinical trials DOI Creative Commons
Yi‐Fan Chen, Frank Luh, Yuan‐Soon Ho

и другие.

Journal of Biomedical Science, Год журнала: 2024, Номер 31(1)

Опубликована: Июль 11, 2024

Abstract Exosomes are extracellular vesicles generated by all cells and they carry nucleic acids, proteins, lipids, metabolites. They mediate the exchange of substances between cells,thereby affecting biological properties activities recipient cells. In this review, we briefly discuss composition exocomes exosome isolation. We also review clinical applications exosomes in cancer biology as well strategies exosome-mediated targeted drug delivery systems. Finally, application context therapeutics both practice literature discussed.

Язык: Английский

Процитировано

31

Extracellular Vesicle Preparation and Analysis: A State‐of‐the‐Art Review DOI Creative Commons
Zesheng Wang, Xiaoyu Zhou, Qinglong Kong

и другие.

Advanced Science, Год журнала: 2024, Номер 11(30)

Опубликована: Июнь 14, 2024

Abstract In recent decades, research on Extracellular Vesicles (EVs) has gained prominence in the life sciences due to their critical roles both health and disease states, offering promising applications diagnosis, drug delivery, therapy. However, inherent heterogeneity complex origins pose significant challenges preparation, analysis, subsequent clinical application. This review is structured provide an overview of biogenesis, composition, various sources EVs, thereby laying groundwork for a detailed discussion contemporary techniques preparation analysis. Particular focus given state‐of‐the‐art technologies that employ microfluidic non‐microfluidic platforms EV processing. Furthermore, this discourse extends into innovative approaches incorporate artificial intelligence cutting‐edge electrochemical sensors, with particular emphasis single proposes current outlines prospective avenues future research. The objective motivate researchers innovate expand methods analysis fully unlocking biomedical potential.

Язык: Английский

Процитировано

27

Cell Type-Specific Extracellular Vesicles and Their Impact on Health and Disease DOI Open Access
Sohil Amin,

Hamed Massoumi,

Deepshikha Tewari

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 2730 - 2730

Опубликована: Фев. 27, 2024

Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability selectively transfer biomolecules specific cell types. EVs, composed proteins, nucleic acids, and lipids, taken up by cells affect variety signaling cascades. Research the field has primarily focused on stem with particular focus mesenchymal cells, for potential therapeutic benefits. Recently, tissue-specific EVs or type-specific extracellular (CTS-EVs), have garnered attention unique biogenesis molecular composition because they enable highly targeted cell-specific communication. Various studies outlined roles that CTS-EVs play physiological function maintenance homeostasis, including immune modulation, tissue regeneration, organ development. These properties also exploited disease propagation, such as cancer, neurological disorders, infectious diseases, autoimmune conditions, more. The insights gained from analyzing different biological not only enhance our understanding pathogenesis but open new avenues innovative diagnostic biomarkers targets wide spectrum medical conditions. This review comprehensively outlines current CTS-EV origins, within normal physiology, implications diseased states.

Язык: Английский

Процитировано

20

The application of exosomes and Exosome-nanoparticle in treating brain disorders DOI
Soodeh Salarpour, Mahmood Barani, Abbas Pardakhty

и другие.

Journal of Molecular Liquids, Год журнала: 2022, Номер 350, С. 118549 - 118549

Опубликована: Янв. 19, 2022

Язык: Английский

Процитировано

68

Biomarkers of Neurodegenerative Diseases: Biology, Taxonomy, Clinical Relevance, and Current Research Status DOI Creative Commons
Dorota Koníčková, Kateřina Menšíková, Lucie Tučková

и другие.

Biomedicines, Год журнала: 2022, Номер 10(7), С. 1760 - 1760

Опубликована: Июль 21, 2022

The understanding of neurodegenerative diseases, traditionally considered to be well-defined entities with distinguishable clinical phenotypes, has undergone a major shift over the last 20 years. diagnosis diseases primarily requires functional brain imaging techniques or invasive tests such as lumbar puncture assess cerebrospinal fluid. A new biological approach and research efforts, especially in vivo, have focused on biomarkers indicating underlying proteinopathy fluid blood serum. However, due complexity heterogeneity processes within central nervous system large number overlapping diagnoses, identifying individual proteinopathies is relatively difficult often not entirely accurate. For this reason, there an urgent need develop laboratory methods for specific biomarkers, understand molecular basis disorders classify quantifiable readily available tools that can accelerate efforts translate knowledge into disease-modifying therapies improve simplify areas differential diagnosis, well monitor disease course aim estimating prognosis evaluating effects treatment. review summarize current about clinically relevant different diseases.

Язык: Английский

Процитировано

58