Progranulin reduces insoluble TDP-43 levels, slows down axonal degeneration and prolongs survival in mutant TDP-43 mice

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

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ConclusionsThe present work is the first in vivo FDG-PET study showing the heterogeneous patterns of brain regional hypo- and hypermetabolism in single patients sharing C9orf72 mutation. Brain hypometabolism was consistent with the clinical phenotypes, supporting the diagnostic importance of neuroimaging functional biomarkers to capture at single-subject level specific brain dysfunction.
Source: Neurological Sciences - Category: Neurology Source Type: research
Mary Kay Floeter, Tania F. Gendron
Source: Frontiers in Neurology - Category: Neurology Source Type: research
The multidomain scaffold protein p62 (also called sequestosome-1) is involved in autophagy, antimicrobial immunity, and oncogenesis. Mutations in SQSTM1, which encodes p62, are linked to hereditary inflammatory conditions such as Paget’s disease of the bone, frontotemporal dementia (FTD), amyotrophic lateral sclerosis, and distal myopathy with rimmed vacuoles. Here, we report that p62 was proteolytically trimmed by the protease caspase-8 into a stable protein, which we called p62TRM. We found that p62TRM, but not full-length p62, was involved in nutrient sensing and homeostasis through the mechanistic target of rapam...
Source: Signal Transduction Knowledge Environment - Category: Science Authors: Tags: STKE Research Articles Source Type: news
Abstract The multidomain scaffold protein p62 (also called sequestosome-1) is involved in autophagy, antimicrobial immunity, and oncogenesis. Mutations in SQSTM1, which encodes p62, are linked to hereditary inflammatory conditions such as Paget's disease of the bone, frontotemporal dementia (FTD), amyotrophic lateral sclerosis, and distal myopathy with rimmed vacuoles. Here, we report that p62 was proteolytically trimmed by the protease caspase-8 into a stable protein, which we called p62TRM We found that p62TRM, but not full-length p62, was involved in nutrient sensing and homeostasis through the mechanistic targ...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research
The ubiquitin-like protein ubiquilin 2 (UBQLN2) has been genetically and pathologically linked to the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but its normal cellular functions are not well understood. In a search for UBQLN2-interacting proteins, we found an enrichment of stress granule (SG) components, including ALS/FTD-linked...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: PNAS Plus Source Type: research
ConclusionsThis study enlarges the genetic and phenotypic spectrum ofTBK1 mutation in a Chinese cohort. Our data indicates thatTBK1 mutation is not a common cause for ALS and FTD in Chinese patients.
Source: Translational Neurodegeneration - Category: Neurology Source Type: research
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Source: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration - Category: Neurology Authors: Source Type: research
Publication date: Available online 24 November 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Junghee Lee, Phuong T. Nguyen, Hyun-Soo Shim, Seung Jae Hyeon, Hyeonjoo Im, Mi-Hyun Choi, Sooyoung Chung, Neil W. Kowall, Sean Bong Lee, Hoon RyuAbstractEwing's sarcoma (EWS) is a bone cancer arising predominantly in young children. EWSR1 (Ewing Sarcoma breakpoint region 1/EWS RNA binding protein 1) gene is ubiquitously expressed in most cell types, indicating it has diverse roles in various cellular processes and organ development. Recently, several studies have shown that missense mutation...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
In this study, angiopoietin-1, an endothelial growth factor crucial for vascular development and angiogenesis, and the integrin αvβ3 binding peptide C16, which inhibits inflammatory cell infiltration, were utilized to improve the local microenvironment within the central nervous system of an ALS/PDC rodent model by minimizing inflammation. Our results revealed that L-serine application yielded better effects than C16+ angiopoietin-1 treatment alone for alleviating apoptotic and autophagic changes and improving cognition and electrophysiological dysfunction, but not for improving the inflammatory micro-environmen...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
Authors: Papadopoulou A, Oertel FC, Zimmermann H, Zeitz O, Brandt AU, Paul F Abstract Retinal changes and visual symptoms are present in several inflammatory, degenerative and tumorous disorders of the central nervous system (CNS). Optical coherence tomography (OCT) is a method that can be used in clinical practice to detect and quantify the structural correlates of these visual symptoms in neurological disorders. OCT is a non-invasive imaging technique, based on interferometry, which can create high-resolution images of the retina and measure the thickness and volume of the different retinal layers. The combined g...
Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
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