Pathomechanisms of TDP ‐43 in neurodegeneration

This article is protected by copyright. All rights reserved.
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Review Source Type: research

Related Links:

Abstract Abnormal protein aggregation is a common pathological feature of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Protein posttranslational modifications (PTMs) play a crucial regulatory role in the formation of pathologic aggregation. Among the known PTMs involved in neurodegeneration, poly(ADP-ribosylation) (PARylation) has emerged with promising therapeutic potentials of the use of poly(ADP-ribose) (PAR) polymerase (PARP) inhibitors. In this review, we describe the mounting evidence that abnormal PA...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research
Conclusion and Future Aspects This review summarizes available NTF expression data, compiles existing evidence on the effects of glial NTF signaling in healthy conditions and in disease models (Figure 1), and highlights the importance of this topic for future studies. The relationship between NTFs and glia is crucial for both the developing and adult brain. While some of these factors, such as NT-3 and CNTF, have highly potent effects on gliogenesis, others like BDNF and GDNF, are important for glia-mediated synapse formation. Neurotrophic factors play significant roles during neurodegenerative disorders. In many cases, ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusion The key problem with the ND field is the lack of understanding in the events preceding the development of protein-based markers – such as Tau – currently used to diagnose NDs. By this stage, the diseases become more difficult to treat. SncRNAs play an important regulatory role in the maintenance of the homeostatic brain. Therefore, changes in their concentration levels can be indicative of mechanistic changes that could precede protein-based markers. One single sncRNA biomarker is unlikely to differentiate between diseases. However, a combination of sncRNA biomarkers could be illustrative of the me...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
This study was carried out in accordance with the recommendations of the National Animal Care and Use Committee of the University of Buenos Aires (CICUAL). The protocol was approved by the CICUAL. Mice were kept under a 12-h light/dark cycle, with controlled temperature (23 ± 2°C) and humidity (40–60%) and had ad libitum access to food and water. To produce hTDP-43 transgenic lines, as described previously (Igaz et al., 2011), pronucleus of fertilized eggs from C57BL/6J × C3HeJ F1 matings were injected with a vector containing hTDP-43-WT cDNA. Monogenic tetO-TDP-WT12 mice wer...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Silvia Pregnolato1*, Elavazhagan Chakkarapani1, Anthony R. Isles2 and Karen Luyt1 1Department of Neonatal Neurology, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom 2Behavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom Preterm birth complications are the leading cause of child death worldwide and a top global health priority. Among the survivors, the risk of life-long disabilities is high, including cerebral palsy and impairment of movement, cognition, and behavior. U...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Kukreti Oxidative stress is proposed as a regulatory element in ageing and various neurological disorders. The excess of oxidants causes a reduction of antioxidants, which in turn produce an oxidation–reduction imbalance in organisms. Paucity of the antioxidant system generates oxidative-stress, characterized by elevated levels of reactive species (oxygen, hydroxyl free radical, and so on). Mitochondria play a key role in ATP supply to cells via oxidative phosphorylation, as well as synthesis of essential biological molecules. Various redox reactions catalyzed by enzymes take place in the oxidative phosphoryl...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
Conclusions In this review, we analyzed mechanisms through which mitobolites, a distinct set of mitochondria-generated metabolites, can be released from mitochondria and then act as second messengers that contribute to cellular and organismal aging by regulating longevity-defining processes outside of mitochondria. Our analysis indicates that in eukaryotes across phyla, these second messengers of cellular aging exhibit the following common features: (1) they are produced in mitochondria in response to certain changes in the nutrient, stress, proliferation or age status of the cell; it remains unknown, however, what kind o...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
In this study, we used a monosynaptic rabies tracing technique to label the whole-brain inputs to specific cell types in the MOp and MOs simultaneously in a same transgenic mouse. First, 150 nl AAV helper mixtures were injected into the ipsilateral MOp (AP:1.54 mm, ML:1.70 mm, DV:-1.50 mm) and MOs (AP:1.54 mm, ML:0.50 mm, DV:-1.35 mm) in Thy1-cre or Vgat-cre mice respectively, mixed with rAAV2/9-Ef1α-DIO-BFP-2a-TVA-WPRE-pA and rAAV2/9-Ef1α-DIO-RG-WPRE-pA as the ratio of 1:2. Three weeks later, 300 nl RV-ΔG-EnVA-EGFP and RV-ΔG-EnVA-Dsred were injected into the two subregions of the MC respectively. O...
Source: Frontiers in Neuroanatomy - Category: Neurology Source Type: research
Conclusions: We demonstrated in the SOD1G93A model of ALS that increased levels of several cytokines were associated with a shorter lifespan. However, their role as prognostic biomarkers is unclear as their expression was very variable depending on both the disease stage and the subject. Nevertheless, cytokines may be potential therapeutic targets. Introduction Amyotrophic Lateral Sclerosis (ALS) is one of the most common rare diseases of unknown origin that leads to progressive motor neuron degeneration and muscle denervation (1). In particular, it has been described that either distal axonopathy or neuromuscular ju...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
We present evidence from previous works on the important phenotypic changes of various neuronal types in these neurological diseases. We also summarize efforts on conducting low- and high-throughput screening experiments with hiPSCs toward developing potential therapeutics for treatment of neurodegenerative diseases. Lastly, we discuss the limitations of hiPSCs culture system in studying neurodegenerative diseases and alternative strategies to overcome these drawbacks.
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
More News: ALS | Alzheimer's | Brain | Genetics | Huntington's Disease | Neurology | Neuroscience | Parkinson's Disease | Study