No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients

We evaluated the genetic contribution of the T cell-restricted intracellular antigen-1 gene (TIA1) in a European cohort of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) patients. Exonic resequencing of TIA1 in 1120 patients (693 FTD, 341 ALS, 86 FTD-ALS) and 1039 controls identified in total five rare heterozygous missense variants, affecting the TIA1 low-complexity domain (LCD). Only one missense variant, p.Met290Thr, identified in a familial FTD patient with disease onset at 64 years, was absent from controls yet received a CADD score of 11.42.
Source: Neurobiology of Aging - Category: Neuroscience Authors: Tags: Negative results Source Type: research

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Publication date: Available online 16 October 2018Source: Journal of Neuroscience MethodsAuthor(s): Wilson BarnabasAbstractBrain specific drug delivery is one of the most interesting and challenging areas of research. The blood-brain barrier separates the brain from blood and acts as a barrier to protect the brain from microorganisms, neurotoxins and chemical substances. But, the same mechanism poses an obstacle for the entry of many drugs into the brain. Worldwide, approximately 1.5 billion people are suffering from CNS disorders, such as Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophi...
Source: Journal of Neuroscience Methods - Category: Neuroscience Source Type: research
TAR DNA binding protein 43 (TDP-43) is the main disease protein in most patients with amyotrophic lateral sclerosis (ALS) and about 50% of patients with frontotemporal dementia (FTD). TDP-43 pathology is not r...
Source: Molecular Neurodegeneration - Category: Neurology Authors: Tags: Research article Source Type: research
In this study, we attempted to delineate the aggregation-prone sequences of the structural domain of TDP-43. Here, we investigated the self-assembly of peptides of TDP-43 using aggregation prediction algorithms, Zipper DB and AMYLPRED2. The three aggregation-prone peptides identified were from N-terminal domain (24GTVLLSTV31), and RNA recognition motifs, RRM1 (128GEVLMVQV135) and RRM2 (247DLIIKGIS254). Furthermore, the amyloid fibril forming propensities of these peptides were analyzed through different biophysical techniques and molecular dynamics simulation. Our study shows the different aggregation ability of conserved ...
Source: Biochimica et Biophysica Acta (BBA) Proteins and Proteomics - Category: Biochemistry Source Type: research
ConclusionsTherefore, we have demonstrated FUS as a modulator of circadian gene expression, and provided novel mechanistic insights into the mutual influence between circadian control and neurodegeneration-associated proteins.
Source: Translational Neurodegeneration - Category: Neurology Source Type: research
TAR DNA-binding protein of 43 kDa (TDP-43) forms pathological aggregates in neurodegenerative diseases, particularly in certain forms of frontotemporal dementia and amyotrophic lateral sclerosis. Pathological modifications of TDP-43 include proteolytic fragmentation, phosphorylation, and ubiquitinylation. A pathognomonic TDP-43 C-terminal fragment (CTF) spanning amino acids 193–414 contains only four lysine residues that could be potentially ubiquitinylated. Here, serial mutagenesis of these four lysines to arginine revealed that not a single residue is responsible for the ubiquitinylation of mCherry-tagged CTF. Remo...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Molecular Bases of Disease Source Type: research
OBJECTIVE: The aim of this study was to determine in a systematic manner if the C9orf72 phenotype might extend beyond frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) to include psychiatric disease. METHODS: A validated ...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Suicide and Self-Harm Source Type: news
Brain magnetic resonance elastography (MRE) was developed on the basis of a desire to “palpate by imaging” and is becoming a powerful tool in the investigation of neurophysiological and neuropathological states. Measurements are acquired with a specialized MR phase-contrast pulse sequence that can detect tissue motion in response to an applied external or internal excitation. The tissue viscoelasticity is then reconstructed from the measured displacement. Quantitative characterization of brain viscoelastic behaviors provides us an insight into the brain structure and function by assessing the mechanical rigidit...
Source: Topics in Magnetic Resonance Imaging - Category: Radiology Tags: Review Articles Source Type: research
AbstractThe advent of next-generation sequencing has changed genetic diagnostics, allowing clinicians to test concurrently for phenotypically overlapping conditions such as Alzheimer ’s disease (AD) and frontotemporal dementia (FTD). However, to interpret genetic results, clinicians require an understanding of the benefits and limitations of different genetic technologies, such as the inability to detect large repeat expansions in such diseases asC9orf72-associated FTD and amyotrophic lateral sclerosis. Other types of mutations such as large deletions or duplications and triple repeat expansions may also go undetecte...
Source: Molecular Diagnosis and Therapy - Category: Molecular Biology Source Type: research
Although several studies have reported a link between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and mental disorders, few investigations have focused on very early-onset psychosis (onset before age 13 years).
Source: Journal of the American Academy of Child and Adolescent Psychiatry - Category: Psychiatry Authors: Source Type: research
In this study, we found that TXNIP deficiency induces accelerated senescent phenotypes of mouse embryonic fibroblast (MEF) cells under high glucose condition and that the induction of cellular ROS or AKT activation is critical for cellular senescence. Our results also revealed that TXNIP inhibits AKT activity by a direct interaction, which is upregulated by high glucose and H2O2 treatment. In addition, TXNIP knockout mice exhibited an increase in glucose uptake and aging-associated phenotypes including a decrease in energy metabolism and induction of cellular senescence and aging-associated gene expression. We propose that...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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