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Role of tRNA-Derived Fragments in Neurological Disorders: a Review
AbstracttRFs are small tRNA derived fragments that are emerging as novel therapeutic targets and regulatory molecules in the pathophysiology of various neurological disorders. These are derived from precursor or mature tRNA, forming different subtypes that have been reported to be involved in neurological disorders like stroke, Alzheimer ’s, epilepsy, Parkinson’s, MELAS, autism, and Huntington’s disorder. tRFs were earlier believed to be random degradation debris of tRNAs. The significant variation in the expression level of tRFs in disease conditions indicates their salient role as key players in regulation of these...
Source: Molecular Neurobiology - January 19, 2023 Category: Neurology Source Type: research

Direct AT2R Stimulation Slows Post-stroke Cognitive Decline in the 5XFAD Alzheimer ’s Disease Mice
AbstractAlzheimer ’s disease (AD), currently the single leading cause of death still on the rise, almost always coexists alongside vascular cognitive impairment (VCI). In fact, the ischemic disease affects up to 90% of AD patients, with strokes and major infarctions representing over a third of vascular lesions. St udies also confirmed that amyloid plaques, typical of AD, are much more likely to cause dementia if strokes or cerebrovascular damage also exist, leading to the term “mixed pathology” cognitive impairment. Although its incidence is expected to grow, there are no satisfactory treatments. There is hence an u...
Source: Molecular Neurobiology - June 5, 2022 Category: Neurology Source Type: research

Generation and Role of Calpain-Cleaved 17-kDa Tau Fragment in Acute Ischemic Stroke
In this study, we observed the accumulation of 17-kDa tau fragment in cultured primary neurons and media after oxygen-glucose deprivation/reperfusion (OGD/R) treatment that could be diminished by the presence of a calpain inhibitor. This calpa in-mediated proteolytic tau fragment was also detected in brain tissues from middle cerebral artery occlusion–injured rats and acute ischemic stroke patients receiving strokectomy, and human plasma samples collected within 48 h after the onset of stroke. The mass spectrometry analysis of this 17-k Da fragment identified 2 peptide sequences containing 195–224 amino acids of tau, w...
Source: Molecular Neurobiology - August 19, 2021 Category: Neurology Source Type: research

Targeting of Perforin Inhibitor into the Brain Parenchyma Via a Prodrug Approach Can Decrease Oxidative Stress and Neuroinflammation and Improve Cell Survival
AbstractThe cytolytic protein perforin has a crucial role in infections and tumor surveillance. Recently, it has also been associated with many brain diseases, such as neurodegenerative diseases and stroke. Therefore, inhibitors of perforin have attracted interest as novel drug candidates. We have previously reported that converting a perforin inhibitor into an L-type amino acid transporter 1 (LAT1)-utilizing prodrug can improve the compound ’s brain drug delivery not only across the blood–brain barrier (BBB) but also into the brain parenchymal cells: neurons, astrocytes, and microglia. The present study evaluated whet...
Source: Molecular Neurobiology - September 24, 2020 Category: Neurology Source Type: research

Novel miRNA PC-5P-12969 in Ischemic Stroke
AbstractCirculating microRNAs (miRNAs) have been used effectively as peripheral biomarkers and mechanistic targets for human diseases such as stroke, Alzheimer ’s, and cancer. The purpose of our study is to determine noninvasive, blood-based early detectable biomarkers for ischemic stroke (IS). Based on our previous global miRNA sequencing study, four miRNAs were previously unreported (novel) in IS condition. Among these, miRNA PC-5P-12969 was exclusivel y expressed in the IS condition; otherwise, it was not expressed in normal condition, and therefore, we focused on miRNA PC-5P-12969 for further studies. In the present ...
Source: Molecular Neurobiology - April 4, 2019 Category: Neurology Source Type: research

Angiotensin Receptor Blockade by Inhibiting Glial Activation Promotes Hippocampal Neurogenesis Via Activation of Wnt/ β-Catenin Signaling in Hypertension
AbstractHypertension is one of the major risk factors for central nervous system (CNS) disorders like stroke and Alzheimer ’s disease (AD). On the other hand, CNS diseases like AD have been associated with gliosis and impaired neurogenesis. Further, renin angiotensin system (RAS) is intricately associated with hypertension; however, the accumulating evidences suggest that over-activity of RAS may perpetuate the brain inflammation related with AD. Therefore, in the present study, we examined the effect of hypertension and RAS on glial (astrocytes and microglia) activation and hippocampal neurogenesis in a rat model of chr...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Thioredoxin-Interacting Protein (TXNIP) in Cerebrovascular and Neurodegenerative Diseases: Regulation and Implication
AbstractNeurological diseases, including acute attacks (e.g., ischemic stroke) and chronic neurodegenerative diseases (e.g., Alzheimer ’s disease), have always been one of the leading cause of morbidity and mortality worldwide. These debilitating diseases represent an enormous disease burden, not only in terms of health suffering but also in economic costs. Although the clinical presentations differ for these diseases, a growing body of evidence suggests that oxidative stress and inflammatory responses in brain tissue significantly contribute to their pathology. However, therapies attempting to prevent oxidative damage o...
Source: Molecular Neurobiology - February 27, 2018 Category: Neurology Source Type: research

Protective Effects of Spatholobi Caulis Extract on Neuronal Damage and Focal Ischemic Stroke/Reperfusion Injury
AbstractNeuronal apoptotic cell death plays an important role in many neurological disorders, including Alzheimer ’s disease, Parkinson’s disease, and ischemic stroke. Spatholobi Caulis (SC) has been widely used in traditional herbal medicine for the treatment of cancer, inflammation, viral infection, and anemia. However, the protective effects of SC extract (SCE) against apoptotic cell death in the brain h ave not been reported. We investigated the protective effects of SCE against neuronal injury etoposide-induced neurotoxicity and in rats subjected to focal transient ischemic stroke middle cerebral artery occlusion ...
Source: Molecular Neurobiology - July 13, 2017 Category: Neurology Source Type: research

Bone Marrow-Derived Endothelial Progenitor Cells Protect Against Scopolamine-Induced Alzheimer-Like Pathological Aberrations
Abstract Vascular endothelial dysfunction plays a key role in the pathogenesis of Alzheimer’s disease (AD). Patients with AD have displayed decreased circulating endothelial progenitor cells (EPCs) which repair and maintain the endothelial function. Transplantation of EPCs has emerged as a promising approach for the management of cerebrovascular diseases including ischemic stroke, however, its impact on AD has been poorly described. Thus, the current study aimed at investigating the effects of bone marrow-derived (BM) EPCs transplantation in repeated scopolamine-induced cognitive impairment, an experimental mode...
Source: Molecular Neurobiology - December 20, 2014 Category: Neurology Source Type: research

From Chemotherapy-Induced Emesis to Neuroprotection: Therapeutic Opportunities for 5-HT 3 Receptor Antagonists
Abstract 5-HT3 receptor antagonists are extensively used as efficacious agents in counteracting chemotherapy-induced emesis. Recent investigations have shed light on other potential effects (analgesic, anxiolytic, and anti-psychotic). Some studies have reported neuroprotective properties for the 5-HT3 receptor antagonists in vitro and in vivo. When administered to Aβ-challenged rat cortical neurons, 5-HT3 receptor antagonists substantially abated apoptosis, elevation of cytosolic Ca2, glutamate release, reactive oxygen species (ROS) generation, and caspase-3 activity. In addition, in vivo studies show that 5-HT3 ...
Source: Molecular Neurobiology - November 7, 2014 Category: Neurology Source Type: research