Importance of the subcellular location of protein deposits in neurodegenerative diseases.

Importance of the subcellular location of protein deposits in neurodegenerative diseases. Curr Opin Neurobiol. 2018 Apr 06;51:127-133 Authors: Bertolotti A Abstract Alzheimer's disease, Parkinson's, Huntington's, amyotrophic lateral sclerosis (ALS) and prion disorders are devastating neurodegenerative diseases of increasing prevalence in aging populations. Although clinically different, they share similar molecular features: the accumulation of one or two proteins in abnormal conformations inside or outside neurons. Enhancing protein quality control systems could be a useful strategy to neutralize the abnormal proteins causing neurodegenerative diseases. This review emphasizes the subcellular location of protein deposits in neurodegenerative diseases and the need to tailor strategies aimed at boosting protein quality control systems to the affected subcellular compartment. Inhibition of a protein phosphatase terminating the unfolded protein response will be discussed as a strategy to protect from diseases associated with misfolded proteins in the endoplasmic reticulum. PMID: 29631171 [PubMed - as supplied by publisher]
Source: Current Opinion in Neurobiology - Category: Neurology Authors: Tags: Curr Opin Neurobiol Source Type: research

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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
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Regulation of autophagy has been a tremendously popular topic in the aging research community over the past twenty years, so much so that it is very surprising that little progress towards clinical therapies has been made. Search PubMed for autophagy and aging and you'll find a deluge of papers over this time frame, many of which express optimism on the topic of finding ways to upregulate autophagy to improve health and slow the aging process. It is the consensus in the research community that autophagy declines with age, and that there are benefits to be realized through increased autophagy. This may allow many age-relate...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Publication date: Available online 24 January 2019Source: NeuroscienceAuthor(s): P.C. Bello-Medina, R.A. Prado-Alcalá, S. Rivas-ArancibiaAbstractThe growth of many cities has generated an increase in the emission of environmental pollutants. Exposure to these pollutants has been associated with increased mortality worldwide. These pollutants, such as ozone, produce reactive oxygen species (ROS), which cause oxidative stress throughout the body. It has been observed that there is a relationship between chronic oxidative stress and the development of degenerative diseases typical of old age such as amyotrophic lateral...
Source: Neuroscience - Category: Neuroscience Source Type: research
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