New pathologic mechanisms in nucleotide repeat expansion disorders.

New pathologic mechanisms in nucleotide repeat expansion disorders. Neurobiol Dis. 2019 Jun 20;:104515 Authors: Rodriguez CM, Todd PK Abstract Tandem microsatellite repeats are common throughout the human genome and intrinsically unstable, exhibiting expansions and contractions both somatically and across generations. Instability in a small subset of these repeats are currently linked to human disease, although recent findings suggest more disease-causing repeats await discovery. These nucleotide repeat expansion disorders (NREDs) primarily affect the nervous system and commonly lead to neurodegeneration through toxic protein gain-of-function, protein loss-of-function, and toxic RNA gain-of-function mechanisms. However, the lines between these categories have blurred with recent findings of unconventional Repeat Associated Non-AUG (RAN) translation from putatively non-coding regions of the genome. Here we review two emerging topics in NREDs: 1) The mechanisms by which RAN translation occurs and its role in disease pathogenesis and 2) How nucleotide repeats as RNA and translated proteins influence liquid-liquid phase separation, membraneless organelle dynamics, and nucleocytoplasmic transport. We examine these topics with a particular eye on two repeats: the CGG repeat expansion responsible for Fragile X syndrome and Fragile X-associated Tremor Ataxia Syndrome (FXTAS) and the intronic GGGGCC repeat expansion in C9orf72, the most common inherited cause of ...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research

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iad Fajloun Apitherapy is an alternate therapy that relies on the usage of honeybee products, most importantly bee venom for the treatment of many human diseases. The venom can be introduced into the human body by manual injection or by direct bee stings. Bee venom contains several active molecules such as peptides and enzymes that have advantageous potential in treating inflammation and central nervous system diseases, such as Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis. Moreover, bee venom has shown promising benefits against different types of cancer as well as ant...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
Park Carotid intima-media thickness (CIMT) has been proposed as a surrogate marker of cardiovascular disease. Mild cognitive impairment (MCI) and pre-frailty are reportedly associated with increased CIMT. As the evidence on the association of CIMT with combinations of MCI and pre-frailty is limited, this association is examined. A total of 231 older adults participated. MCI was defined according to clinical consensus or psychometric criteria by a dementia specialist, and considering detailed neuropsychological assessments. Also, pre-frailty was defined as subjects with frail component of 1 or 2. Carotid variables were...
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Article Source Type: research
AbstractFrontotemporal dementia (FTD) is a neurodegenerative brain disorder primarily affecting the frontal and/or temporal lobes. Three main subtypes have been recognized: behavioural-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA), each of which has a distinct clinical and cognitive profile. Although the role of the cerebellum in cognition is increasingly accepted, knowledge of cerebellar changes across neuroimaging modalities and their contribution to behavioural and cognitive changes in FTD syndromes is currently scant. We conducted an anatomical/activation likelihood estimation (A...
Source: Neuropsychology Review - Category: Neuroscience Source Type: research
Publication date: Available online 18 August 2019Source: Alzheimer's &DementiaAuthor(s): Binyin Li, Yixi He, Jianfang Ma, Pei Huang, Juanjuan Du, Li Cao, Yan Wang, Qin Xiao, Huidong Tang, Shengdi ChenAbstractObjectiveGut microbiota changes before the onset of Alzheimer's disease (AD) and the alterations could be detected in the stage of mild cognitive impairment (MCI). The findings might offer diagnostic biomarkers before the onset of dementia.BackgroundAD is the most common cause of dementia, and MCI is the predementia state. Recent studies suggest the alterations in the gut microbial communities associated with AD, w...
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - Category: Geriatrics Source Type: research
In conclusions, nicergoline appears to delay the speed of deterioration of cognitive function in patients with PDD based on our observation of decreased rCBF in the temporal regions and inferior frontal regions of PDD − N patients compared to PDD + N patients after 12-month of nicergoline therapy. Therefore, we cautiously suggest that nicergoline administration in PDD patients may slow progression of cognitive impairment in affected brain regions.
Source: Journal of Clinical Neuroscience - Category: Neuroscience Source Type: research
In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Publication date: 17 August 2019Source: New Scientist, Volume 243, Issue 3243Author(s): Clare Wilson
Source: New Scientist - Category: Science Source Type: research
This report presents a novel technique termed the pharyngeal clearance maneuver, which uses a modified application of the mechanical insufflation-exsufflation device to mobilize “secretion burden” at the portion of the trachea above the tracheostomy cuff during cuff deflation. Utilization of this strategy may reduce the risk of aspiration, infection, and respiratory compromise for patients with high cervical spinal cord injury in the acute rehabilitation setting. It is of particular benefit for those whose cuffs are being deflated for the first time and who may have large secretion volumes above the cuff. It ca...
Source: American Journal of Physical Medicine and Rehabilitation - Category: Rehabilitation Tags: Brief Reports Source Type: research
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Henry Paulson More than 40 diseases, most of which primarily affect the nervous system, are caused by expansions of simple sequence repeats dispersed throughout the human genome. Expanded trinucleotide repeat diseases were discovered first and remain the most frequent. More recently tetra-, penta-, hexa-, and even dodeca-nucleotide repeat expansions have been identified as the cause of human disease, including some of the most common genetic disorders seen by neurologists. Repeat expansion diseases include both causes of myotonic dystrophy...
Source: Handbook of Clinical Neurology - Category: Neurology Source Type: research
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