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It has been widely established that the characterization of extracellular vesicles (EVs), particularly small EVs (sEVs), shed by different cell types into biofluids, helps to identify biomarkers and therapeutic targets in neurological and neurodegenerative diseases. Recent studies are also exploring the efficacy of mesenchymal stem cell-derived extracellular vesicles naturally enriched with therapeutic microRNAs and proteins for treating various diseases. In addition, EVs released by various neural cells play a crucial function in the modulation of signal transmission in the brain in physiological conditions. However, in pathological conditions, such EVs can facilitate the spread of pathological proteins from one brain region to the other. On the other hand, the analysis of EVs in biofluids can identify sensitive biomarkers for diagnosis, prognosis, and disease progression. This review discusses the potential therapeutic use of stem cell-derived EVs in several central nervous system diseases. It lists their differences and similarities and confers various studies exploring EVs as biomarkers. Further advances in EV research in the coming years will likely lead to the routine use of EVs in therapeutic settings.

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This review delves into the groundbreaking impact of induced pluripotent stem cells (iPSCs) and three-dimensional organoid models in propelling forward neuropathology research. With a focus on neurodegenerative diseases, neuromotor disorders, and related conditions, iPSCs provide a platform for personalized disease modeling, holding significant potential for regenerative therapy and drug discovery. The adaptability of iPSCs, along with associated methodologies, enables the generation of various types of neural cell differentiations and their integration into three-dimensional organoid models, effectively replicating complex tissue structures in vitro. Key advancements in organoid and iPSC generation protocols, alongside the careful selection of donor cell types, are emphasized as critical steps in harnessing these technologies to mitigate tumorigenic risks and other hurdles. Encouragingly, iPSCs show promising outcomes in regenerative therapies, as evidenced by their successful application in animal models.

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Inflammation is crucial in diseases, and proteins play a key role in the interplay between innate immunity and pathology. This review explores how proteomics helps understanding this relationship, focusing on diagnosis and treatment. We explore the dynamic innate response and the significance of proteomic techniques in deciphering the complex network of proteins involved in prevalent diseases, including infections, cancer, autoimmune and neurodegenerative disorders. Proteomics identifies key proteins in host-pathogen interactions, shedding light on infection mechanisms and inflammation. These discoveries hold promise for diagnostic tools, therapies, and vaccines. In cancer research, proteomics reveals innate signatures associated with tumor development, immune evasion, and therapeutic response. Additionally, proteomic analysis has unveiled autoantigens and dysregulation of the innate immune system in autoimmunity, offering opportunities for early diagnosis, disease monitoring, and new therapeutic targets. Moreover, proteomic analysis has identified altered protein expression patterns in neurodegenerative diseases like Alzheimer's and Parkinson's, providing insights into potential therapeutic strategies. Proteomics of the innate immune system provides a comprehensive understanding of disease mechanisms, identifies biomarkers, and enables effective interventions in various diseases. Despite still in its early stages, this approach holds great promise to revolutionize innate immunity research and significantly improve patient outcomes across a wide range of diseases.

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BACKGROUND: Neurodegenerative diseases lead to difficulties with functional activities. In Peru, most caregivers are family members. Little is known about the COVID-19 pandemic's effect on caregivers in Peru. METHODS: This was a cross-sectional, prospective study of family caregivers of dependent patients with dementia or Parkinson's Disease in Lima, Peru. A caregiver burden and mental health questionnaire was administered to the caregiver. RESULTS: We enrolled 48 caregivers (65% females, mean ± SD age 49.0 ± 12.3 years); 70% of patients had dementia. Nearly 40% of caregivers reported having full-time jobs, and 82% felt overwhelmed with almost 75% dedicating more time to caregiving during the pandemic. Caregivers perceived patients felt lonelier (52%), had an increase in hallucinations (50%), or forgetfulness (71%) compared to pre-pandemic. CONCLUSIONS: Our study highlights that perceived caregiver burden and patient behavioral symptoms may have been exacerbated during the pandemic. In countries such as Peru, more caregiving resources and interventions are needed.

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OBJECTIVES: The endogenous repairing based on the activation of neural stem cells (NSCs) is impaired by neurodegenerative diseases. The present study aims to characterize human stem cells from the apical papilla (hSCAPs) with features of mesenchymal stem cells (MSCs) and to demonstrate the neuronal differentiation of hSCAPs into NSCs through the formation of three-dimensional (3D) neurospheres, verifying the structural, immunophenotyping, self-renewal, gene expression and neuronal activities of these cells to help further improve NSCs transplantation. METHODOLOGY: The hSCAPs were isolated from healthy impacted human third molar teeth and characterized as MSCs. They were then induced into 3D-neurospheres using a specific neural induction medium. Subsequently, the intra-neurospheral cells were confirmed to be NSCs by the identification of Nissl substance and the analysis of immunofluorescence staining, self-renewal ability, and gene expression of the cells. Moreover, the neuronal activity was investigated using intracellular calcium oscillation. RESULTS: The isolated cells from the human apical papilla expressed many markers of MSCs, such as self-renewal ability and multilineage differentiation. These cells were thus characterized as MSCs, specifically as hSCAPs. The neurospheres induced from hSCAPs exhibited a 3D-floating spheroidal shape and larger neurospheres, and consisted of a heterogeneous population of intra-neurospheral cells. Further investigation showed that these intra-neurospheral cells had Nissl body staining and also expressed both Nestin and SOX2. They presented a self-renewal ability as well, which was observed after their disaggregation. Their gene expression profiling also exhibited a significant amount of NSC markers (NES, SOX1, and PAX6). Lastly, a large and dynamic change of the fluorescent signal that indicated calcium ions (Ca2+) was detected in the intracellular calcium oscillation, which indicated the neuronal activity of NSCs-derived hSCAPs. CONCLUSIONS: The hSCAPs exhibited properties of MSCs and could differentiate into NSCs under 3D-neurosphere generation. The present findings suggest that NSCs-derived hSCAPs may be used as an alternative candidates for cell-based therapy, which uses stem cell transplantation to further treat neurodegenerative diseases.

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Mitochondrial dysfunction is reiteratively involved in the pathogenesis of diverse neurodegenerative diseases. Current in vitro and in vivo approaches support that mitochondrial dysfunction is branded by several molecular and cellular defects, whose impact at different levels including the calcium and iron homeostasis, energetic balance and/or oxidative stress, makes it difficult to resolve them collectively given their multifactorial nature. Mitochondrial transfer offers an overall solution since it contains the replacement of damage mitochondria by healthy units. Therefore, this review provides an introducing view on the structure and energy-related functions of mitochondria as well as their dynamics. In turn, we summarize current knowledge on how these features are deregulated in different neurodegenerative diseases, including frontotemporal dementia, multiple sclerosis, amyotrophic lateral sclerosis, Friedreich ataxia, Alzheimer´s disease, Parkinson´s disease, and Huntington's disease. Finally, we analyzed current advances in mitochondrial transfer between diverse cell types that actively participate in neurodegenerative processes, and how they might be projected toward developing novel therapeutic strategies.

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Neurodegenerative diseases (ND) are characterized, especially, by the progressive loss of neurons, resulting in neuropsychomotor dysfunctions. Even with a high prevalence, NDs are treated with drugs that alleviate the symptoms of patients, but which develop adverse events and still do not inhibit the progression of the disease. Thus, within a new pharmacological perspective, this review aimed to verify the therapeutic potential of natural compounds of marine origin against ND. For this, an integrative review was carried out, according to the PRISMA methodology, which included steps such as: search, pre-selection and inclusion of articles. The results described revealed species such as Acaudina malpodioides, Holothuria scabra and Xylaria sp., which presented important evidence in relation to Alzheimer's, reducing the generation of ROS, presenting neuroprotective effects and reducing the concentration of Aß peptide. Regarding Parkinson's disease (PD), another example of ND, the bioactive compounds from Holothuria scabra and Xylaria sp., showed to be able to reduce the degeneration of dopaminergic neurons, reduce the deposition of alpha synuclein and reduce the formation of Mutant Huntingtin protein (Mhtt). The other marine compounds and bioactive substances are also described in this review. In conclusion, the evaluated studies indicate that compounds of marine origin emerge as a promising source of bioactive compounds, revealing an important therapeutic potential for the treatment of ND.

As doenças neurodegenerativas (ND) são caracterizadas, especialmente, pela perda progressiva de neurônios, resultando em disfunções neuropsicomotoras. Mesmo apresentando uma alta prevalência, as DN são tratadas com medicamentos que aliviam os sintomas dos pacientes, mas que desenvolvem eventos adversos e ainda não inibem a progressão da doença. Assim, dentro de uma nova perspectiva farmacológica, esta revisão teve como objetivo verificar o potencial terapêutico de compostos naturais de origem marinha frente às DN. Para tal, foi realizada uma revisão integrativa, segundo a metodologia PRISMA que compreendeu etapas como: busca, pré-seleção e inclusão dos artigos. Os resultados descritos revelaram espécies como, Acaudina malpodioides, Holothuria scabra e Xylaria sp., que apresentaram importantes evidências em relação ao Alzheimer, reduzindo a geração de ROS, apresentando efeitos neuroprotetores e reduzindo a concentração de peptídeo Aß. Sobre a doença de Parkinson (PD), outro exemplo de ND, os compostos bioativos da Holothuria scabra e da Xylaria sp., mostraram ser capazes de diminuir a degeneração de neurônios dopaminérgicos, reduzir a deposição de alfa sinucleína e reduzir a formação de agregados da proteína Huntingtina mutante (Mhtt). Os outros compostos marinhos e substâncias bioativas também são descritos nesta revisão. Em conclusão, os estudos avaliados indicam que os compostos de origem marinha despontam como uma promissora fonte de compostos bioativos, revelando um importante potencial terapêutico para o tratamento das ND.

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INTRODUCTION: Several studies indicate the role of mesenchymal stem cells (MSCs) as an important tool in regenerative medicine associated with injuries that affect the central nervous system (CNS). The MSCs have the capacity to differentiate into cells of the embryonic tissue, such as the mesoderm. So, these cells can be found in a variety of tissues. Also, the MSCs can release immunomodulatory and neurotrophic factors performance as inflammation mediators operating in injured tissue regeneration. Furthermore, they can differentiate into neural-like cells in vitro. Thereby, because of the high immunomodulatory role of MSCs, this review sought to describe the main immunomodulatory mechanisms performed by MSCs in CNS recovery after tissue injury or neurodegenerative diseases. METHODS: PubMed and ScienceDirect were searched between January 2011 to March 2021, and 43 articles met the criteria of the review. RESULTS: This systematic review indicates that MSCs were used in vivo experimental multiple sclerosis, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, ischemic stroke, and traumatic brain injury. The treatment MSCs were usually from human origin, derived from bone marrow, and administered intravenously. CONCLUSION: It was shown that MSCs, independent from origin or administration pathway, can reduce inflammation and help in the recovery and preservation of injured neural tissue. Thus, the use of MSCs represents a potential therapeutic option in the treatment of neurological disorders mediated by inflammatory processes.

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Healthy brain functioning in mammals requires a continuous fine-tuning of gene expression. Accumulating evidence over the last three decades demonstrates that epigenetic mechanisms and dynamic changes in chromatin organization are critical components during the control of gene transcription in neural cells. Recent genome-wide analyses show that the regulation of brain genes requires the contribution of both promoter and long-distance enhancer elements, which must functionally interact with upregulated gene expression in response to physiological cues. Hence, a deep comprehension of the mechanisms mediating these enhancer-promoter interactions (EPIs) is critical if we are to understand the processes associated with learning, memory and recall. Moreover, the onset and progression of several neurodegenerative diseases and neurological alterations are found to be strongly associated with changes in the components that support and/or modulate the dynamics of these EPIs. Here, we overview relevant discoveries in the field supporting the role of the chromatin organization and of specific epigenetic mechanisms during the control of gene transcription in neural cells from healthy mice subjected to the fear conditioning paradigm, a relevant model to study memory ensemble. Additionally, special consideration is dedicated to revising recent results generated by investigators working with animal models and human postmortem brain tissue to address how changes in the epigenome and chromatin architecture contribute to transcriptional dysregulation in Alzheimer's disease, a widely studied neurodegenerative disease. We also discuss recent developments of potential new therapeutic strategies involving epigenetic editing and small chromatin-modifying molecules (or epidrugs).

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Multiple sclerosis (MS) is a highly disabling, progressive neurodegenerative disease with no curative treatment available. Although significant progress has been made in understanding how MS develops, there remain aspects of disease pathogenesis that are yet to be fully elucidated. In this regard, studies have shown that dysfunctional adenosinergic signaling plays a pivotal role, as patients with MS have altered levels adenosine (ADO), adenosine receptors and proteins involved in the generation and termination of ADO signaling, such as CD39 and adenosine deaminase (ADA). We have therefore performed a literature review regarding the involvement of the adenosinergic system in the development of MS and propose mechanisms by which the modulation of this system can support drug development and repurposing.

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