Normal function of ALS and dementia linked gene determined for the first time

(University of Bath) The normal function of a gene associated with the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) has been determined for the first time by University of Bath scientists.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news

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Conclusions The momentous advances in spinal imaging in ALS suggest the spinal metrics may soon be used as validated diagnostic, monitoring, and prognostic markers, contributing both to individualized patient care and pharmacological trials. Author Contributions ME, GQ, PB, and P-FP contributed equally to the conceptualization, drafting, and revision of the manuscript. Funding Peter Bede is supported by the Health Research Board (HRB—Ireland; HRB EIA-2017-019), the Iris O'Brien Foundation, the Irish Institute of Clinical Neuroscience IICN—Novartis Ireland Research Grant, and the Research Motor Neur...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
(St. Jude Children's Research Hospital) St. Jude Children's Research Hospital scientists have found that the enzymes ULK1 and ULK2 play a key role in breaking down cell structures called stress granules, whose persistence leads to toxic buildup of proteins that kill muscle and brain cells. Such buildup is central to the pathology of three related diseases: inclusion body myopathy (IBM), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
AbstractThe hexanucleotide repeat expansion GGGGCC (G4C2)n in theC9orf72 gene is the most common genetic abnormality associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent findings suggest that dysfunction of nuclear-cytoplasmic trafficking could affect the transport of RNA binding proteins in C9orf72 ALS/FTD. Here, we provide evidence that the RNA editing enzyme adenosine deaminase acting on RNA 2 (ADAR2) is mislocalized in C9orf72 repeat expansion mediated ALS/FTD. ADAR2 is responsible for adenosine (A) to inosine (I) editing of double-stranded RNA, and its function has been shown t...
Source: Acta Neuropathologica - Category: Neurology Source Type: research
In this study, we examined phosphorylated p65 (pp65), which is the activated form of a subunit of nuclear factor-kappa B (NF-κB), in the hippocampus of 21 autopsied cases, including AD, amyotrophic lateral sclerosis cases with optineurin mutation (ALS-OPTN), and a variety of other neurodegenerative disorder cases and normal controls. In all cases, GVDs were immunopositive for pp65. The density of pp65-positive GVDs statistically correlated with that of casein kinase 1 delta (CK1δ), which is known as GVD marker. pp65 was also detected in neurites in AD and ALS-OPTN. The number of neurons with pp65-immunoreactive...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
Abstract Diseases of the motor-conducting system that cause moving disability affect socio-economic activity as well as human dignity. Neurolathyrism, konzo, and amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC) have attracted researchers to study the pathology of motor neuron (MN) diseases such as ALS. I have been studying neurolathyrism, which is caused by overconsumption of a legume grass pea (Lathyrys sativus L.). Among people who consume the legume as a food staple, many developed life-long paraparesis in their legs. β-N-oxalyl-l-α,β- diaminopropionic (l-β-ODAP; BOAA),...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research
Abstract Mutations in the TBK1 (TANK binding kinase 1) gene are causally linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TBK1 phosphorylates the cargo receptors OPTN and SQSTM1 regulating a critical step in macroautophagy/autophagy. Disruption of the autophagic flux leads to accumulation of cytosolic protein aggregates, which are a hallmark of ALS. hiPSC-derived TBK1-mutant motoneurons (MNs) showed reduced TBK1 levels and accumulation of cytosolic SQSTM1-positive aggresomes. By screening a library of nuclear-receptor-agonists for modifiers of the SQSTM1 aggregates, we identified 4-...
Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research
This study defines a new clinically relevant concept of T-cell senescence-mediated inflammatory responses in the pathophysiology of abnormal glucose homeostasis. We also found that T-cell senescence is associated with systemic inflammation and alters hepatic glucose homeostasis. The rational modulation of T-cell senescence would be a promising avenue for the treatment or prevention of diabetes. Intron Retention via Alternative Splicing as a Signature of Aging https://www.fightaging.org/archives/2019/03/intron-retention-via-alternative-splicing-as-a-signature-of-aging/ In recent years researchers have inv...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
The aim of our study was to evaluate the role of mutations in theMAPT gene in patients with pure amyotrophic lateral sclerosis (ALS). A cohort of 120 ALS patients, both sporadic and familial, without cognitive impairment was analyzed by next-generation sequencing with a multiple-gene panel comprising 23 genes, includingMAPT, known to be associated with ALS and frontotemporal dementia. The presence of theC9orf72 expansion was also investigated. Twelve patients had mutations in theSOD1, TARDBP, MATR3, andFUS genes, while 10 patients carried theC9orf72 expansion. One female patient was found to carry the D348G mutation inMAPT...
Source: Neurodegenerative Diseases - Category: Neurology Source Type: research
Stress granules (SGs) are non-membrane-bound RNA-protein granules that assemble through phase separation in response to cellular stress. Disturbances in SG dynamics have been implicated as a primary driver of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), suggesting the hypothesis that these diseases reflect an underlying disturbance in the dynamics and material properties of SGs. However, this concept has remained largely untestable in available models of SG assembly, which require the confounding variable of exogenous stressors. Here we introduce a light-induc...
Source: eLife - Category: Biomedical Science Tags: Cell Biology Source Type: research
Abstract The aim of our study was to evaluate the role of mutations in the MAPT gene in patients with pure amyotrophic lateral sclerosis (ALS). A cohort of 120 ALS patients, both sporadic and familial, without cognitive impairment was analyzed by next-generation sequencing with a multiple-gene panel comprising 23 genes, including MAPT, known to be associated with ALS and frontotemporal dementia. The presence of the C9orf72 expansion was also investigated. Twelve patients had mutations in the SOD1, TARDBP, MATR3, and FUS genes, while 10 patients carried the C9orf72 expansion. One female patient was found to carry t...
Source: Neuro-Degenerative Diseases - Category: Neurology Authors: Tags: Neurodegener Dis Source Type: research
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