264 research outputs found
Introduction to stem cell biology and its role in treating neurologic disorders
No full textRegenerative medicine is an emerging and rapidly evolving field of research and therapeutics aimed to restore, maintain, and improve body functions. In the adult mammalian brain, very few neurons, if any, are generated after disease onset or an injury, and its ability to self-repair is therefore limited. Replacing neurons that are lost during neurodegenerative diseases or due to injury therefore represents one of the major challenges to modern medicine. In this introductory chapter, we describe the basic biology of stem cells and outline how stem cells and cell reprogramming can be utilized to create new neurons for therapeutic purposes that are discussed in detail in other chapters in this handbook
The Use of Defective Herpes Simplex Virus Amplicon Vectors to Modify Neural Cells and the Nervous System
No full textTherapeutic potential of vaccines for Alzheimer’s disease
No full text The pathological hallmarks of Alzheimer’s disease (AD) are amyloid-β (Aβ) plaques and Tau-containing neurofibrillary tangles. Although the relationship between neuronal loss and the presence of plaques/tangles is not well understood, the prevailing Aβ hypothesis posits that excessive accumulation of conformers and assemblies of Aβ protein precedes AD-related dementia and neuronal loss. Consequently, most disease-modifying immunotherapy approaches are directed towards modulating the levels of Aβ. The first AD vaccine clinical trial (AN1792) was suspended after the patients developed meningoencephalitis. In spite of the setback, the trial provided insights to refine development second-generation vaccines, which are attempting to resolve the side effects observed in the trial. This article provides an analysis of these efforts. </jats:p
A retrotransposon storm marks clinical phenoconversion to late-onset Alzheimer's disease.
No full textRecent reports have suggested that the reactivation of otherwise transcriptionally silent transposable elements (TEs) might induce brain degeneration, either by dysregulating the expression of genes and pathways implicated in cognitive decline and dementia or through the induction of immune-mediated neuroinflammation resulting in the elimination of neural and glial cells. In the work we present here, we test the hypothesis that differentially expressed TEs in blood could be used as biomarkers of cognitive decline and development of AD. To this aim, we used a sample of aging subjects (age > 70) that developed late-onset Alzheimer's disease (LOAD) over a relatively short period of time (12-48 months), for which blood was available before and after their phenoconversion, and a group of cognitive stable subjects as controls. We applied our developed and validated customized pipeline that allows the identification, characterization, and quantification of the differentially expressed (DE) TEs before and after the onset of manifest LOAD, through analyses of RNA-Seq data. We compared the level of DE TEs within more than 600,000 TE-mapping RNA transcripts from 25 individuals, whose specimens we obtained before and after their phenotypic conversion (phenoconversion) to LOAD, and discovered that 1790 TE transcripts showed significant expression differences between these two timepoints (logFC ± 1.5, logCMP > 5.3, nominal p value < 0.01). These DE transcripts mapped both over- and under-expressed TE elements. Occurring before the clinical phenoconversion, this TE storm features significant increases in DE transcripts of LINEs, LTRs, and SVAs, while those for SINEs are significantly depleted. These dysregulations end with signs of manifest LOAD. This set of highly DE transcripts generates a TE transcriptional profile that accurately discriminates the before and after phenoconversion states of these subjects. Our findings suggest that a storm of DE TEs occurs before phenoconversion from normal cognition to manifest LOAD in risk individuals compared to controls, and may provide useful blood-based biomarkers for heralding such a clinical transition, also suggesting that TEs can indeed participate in the complex process of neurodegeneration
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