Parkinson's disease is characterized neuropathologically by the degeneration of dopaminergic neurons in the ventral midbrain, the accumulation of α-synuclein (α-syn) aggregates in neurons and chronic neuroinflammation. In the past two decades, in vitro, ex vivo and in vivo studies have consistently shown the involvement of inflammatory responses mediated by microglia and astrocytes, which may be elicited by pathological α-syn or signals from affected neurons and other cell types, and are directly linked to neurodegeneration and disease development. Apart from the prominent immune alterations seen in the CNS, including the infiltration of T cells into the brain, more recent studies have demonstrated important changes in the peripheral immune profile within both the innate and adaptive compartments, particularly involving monocytes, CD4+ and CD8+ T cells.
View Article and Find Full Text PDFParkinson's disease (PD) is the second most prevalent neurodegenerative disease and the most common movement disorder. Although PD etiology is not fully understood, alpha (α)-synuclein is a key protein involved in PD pathology. MicroRNAs (miRNA), small gene regulatory RNAs that control gene expression, have been identified as biomarkers and potential therapeutic targets for brain diseases, including PD.
View Article and Find Full Text PDFNeuroinflammation is a pathological mechanism contributing to neurodegenerative diseases. For in-depth studies of neuroinflammation, several animal models reported reproducing behavioral dysfunctions and cellular pathological mechanisms induced by brain inflammation. One of the most popular models of neuroinflammation is the one generated by lipopolysaccharide exposure.
View Article and Find Full Text PDFC-terminal binding proteins (CtBP) are transcriptional co-repressors regulating gene expression. CtBP promote neuronal survival through repression of pro-apoptotic genes, and may represent relevant targets for neurodegenerative disorders, such as Parkinson's disease (PD). Nevertheless, evidence of the role of CtBP1 and CtBP2 in neurodegeneration are scarce.
View Article and Find Full Text PDFRacial socioeconomic gaps are widened in periods of economic recession. Besides social and institutional factors, black people also struggle with many psychological factors. The literature reports racial-biased complex behaviors and high-level processes that are influenced by economic scarcity.
View Article and Find Full Text PDFSteroids constitute an important class of pharmacologically active molecules, playing key roles in human physiology. Within this group, 16-arylideneandrostane derivatives have been reported as potent anti-cancer agents for the treatment of leukemia, breast and prostate cancers, and brain tumors. Additionally, 5α,6α-epoxycholesterol is an oxysterol with several biological activities, including regulation of cell proliferation and cholesterol homeostasis.
View Article and Find Full Text PDFNeurological disorders are one of the world's leading medical and societal challenges due to the lack of efficacy of the first line treatment. Although pharmacological and non-pharmacological interventions have been employed with the aim of regulating neuronal activity and survival, they have failed to avoid symptom relapse and disease progression in the vast majority of patients. In the last 5 years, advanced drug delivery systems delivering bioactive molecules and neuromodulation strategies have been developed to promote tissue regeneration and remodel neuronal circuitry.
View Article and Find Full Text PDFCOVID-19 is the most impacting global pandemic of all time, with over 600 million infected and 6.5 million deaths worldwide, in addition to an unprecedented economic impact. Despite the many advances in scientific knowledge about the disease, much remains to be clarified about the molecular alterations induced by SARS-CoV-2 infection.
View Article and Find Full Text PDFSpatial control of gene expression is critical to modulate cellular functions and deconstruct the function of individual genes in biological processes. Light-responsive gene-editing formulations have been recently developed; however, they have shown limited applicability in vivo due to poor tissue penetration, limited cellular transfection and the difficulty in evaluating the activity of the edited cells. Here, we report a formulation composed of upconversion nanoparticles conjugated with Cre recombinase enzyme through a photocleavable linker, and a lysosomotropic agent that facilitates endolysosomal escape.
View Article and Find Full Text PDFParkinson's disease is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra with no effective cure available. MicroRNA-124 has been regarded as a promising therapeutic entity for Parkinson's disease due to its pro-neurogenic and neuroprotective roles. However, its efficient delivery to the brain remains challenging.
View Article and Find Full Text PDFPediatr Infect Dis J
August 2022
Sickle cell disease (SCD) was found in 10% of children with bacterial meningitis (BM) in Luanda, 5-fold more than in the general population. BM children with SCD versus BM children without SCD had higher inflammatory markers, more often had pneumococcal meningitis (71% vs. 39%), and either died (39% vs.
View Article and Find Full Text PDFAim: Bacterial meningitis (BM) is a common cause of hearing loss in childhood. Our aim was to investigate bacterial aetiology, hearing impairment and outcome in childhood BM with vs. without otitis media (OM) in Angola.
View Article and Find Full Text PDFRecent advances in technology are expected to increase our current understanding of neuroscience. Nanotechnology and nanomaterials can alter and control neural functionality in both and experimental setups. The intersection between neuroscience and nanoscience may generate long-term neural interfaces adapted at the molecular level.
View Article and Find Full Text PDFBackground: The brain vasculature plays a pivotal role in the inflammatory process by modulating the interaction between blood cells and the neurovascular unit. Argonaute-2 (Ago2) has been suggested as essential for endothelial survival but its role in the brain vasculature or in the endothelial-glial crosstalk has not been addressed. Thus, our aim was to clarify the significance of Ago2 in the inflammatory responses elicited by these cell types.
View Article and Find Full Text PDFBackground: In the era of the re-emergence of syphilis, ocular syphilis has gained attention because its prevalence has increased and it can cause blindness and disability.
Objectives: To investigate the clinical presentation and prognosis of ocular syphilis.
Methods: Prospective study on 53 patients (90 eyes) with ocular syphilis diagnosed at the Santa Casa of Belo Horizonte, Brazil.
Curr Top Behav Neurosci
September 2022
Histamine is a biogenic amine playing a central role in allergy and peripheral inflammatory reactions and acts as a neurotransmitter and neuromodulator in the brain. In the adult, histamine is produced mainly by mast cells and hypothalamic neurons, which project their axons throughout the brain. Thus, histamine exerts a range of functions, including wakefulness control, learning and memory, neurogenesis, and regulation of glial activity.
View Article and Find Full Text PDFC-terminal binding proteins (CtBPs) are transcriptional modulators that can regulate gene expression through the recruitment of a corepressor complex composed of chromatin-modifying enzymes and transcriptional factors. In the brain, CtBPs have been described as regulators of cell proliferation, differentiation, and survival. Nevertheless, the role of CtBPs on postnatal neural stem cells (NSCs) fate is not known yet.
View Article and Find Full Text PDFRetinoids regulate a wide spectrum of cellular functions from the embryo throughout adulthood, including cell differentiation, metabolic regulation, and inflammation. These traits make retinoids very attractive molecules for medical purposes. In light of some of the physicochemical limitations of retinoids, the development of drug delivery systems offers several advantages for clinical translation of retinoid-based therapies, including improved solubilization, prolonged circulation, reduced toxicity, sustained release, and improved efficacy.
View Article and Find Full Text PDFAnimal models of human diseases are crucial experimental tools to investigate the mechanisms involved in disease pathogenesis and to develop new therapies. In spite of the numerous animal models currently available that reproduce several neuropathological features of Parkinson disease (PD), it is challenging to have one that consistently recapitulates human PD conditions in both motor behaviors and biochemical pathological outcomes. Given that, we have implemented a new paradigm to expose rats to a chronic low dose of paraquat (PQ), using osmotic minipumps and characterized the developed pathologic features over time.
View Article and Find Full Text PDFCurr Opin Pharmacol
February 2020
Adult neurogenesis, the process of generation of new functional neurons from neural stem cells, occurs in the subventricular zone and the subgranular zone neurogenic niches. This neurogenic process is tightly controlled by several intrinsic factors, including microRNAs (miRNAs), a class of small non-coding RNAs, which control protein translation. MiRNAs have emerged as important regulators of both embryonic and adult neural stem cells self-renewal and proliferation, neuronal differentiation, migration, maturation and integration into the complex neuronal circuitry.
View Article and Find Full Text PDFBraz J Phys Ther
October 2019
Background: Otitis media (OM) is a common childhood infection that may result in bacterial meningitis (BM). However, OM-associated BM remains poorly characterized. We aimed to study the occurrence, clinical presentation and outcome of this type of childhood BM in Luanda, Angola.
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