Drosophila as a Model System for the Identification of Pharmacological Therapies in Neurodegenerative Diseases

2019 ◽  
pp. 433-467 ◽  
Author(s):  
Cristina Solana-Manrique ◽  
María Dolores Moltó ◽  
Pablo Calap-Quintana ◽  
Francisco José Sanz ◽  
José Vicente Llorens ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Model System

Caenorhabditis elegans as a model system for target identification and drug screening against neurodegenerative diseases

2018 ◽  
Vol 819 ◽  
pp. 169-180 ◽  
Author(s):  
Liang Ma ◽  
Yudan Zhao ◽  
Yuchen Chen ◽  
Biao Cheng ◽  
Anlin Peng ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Neurodegenerative Diseases ◽  
Drug Screening ◽  
Target Identification ◽  
Model System

scholarly journals Sirtuins and Autophagy in Age-Associated Neurodegenerative Diseases: Lessons from the C. elegans Model

2021 ◽  
Vol 22 (22) ◽  
pp. 12263
Author(s):  
Anam Naseer ◽  
Snober Shabnam Mir ◽  
Krisztina Takacs-Vellai ◽  
Aamir Nazir
Keyword(s):  
Neurodegenerative Diseases ◽  
Histone Deacetylases ◽  
Vital Role ◽  
Model System ◽  
Dependent Manner ◽  
Class Iii ◽  
C Elegans ◽  
Cell Death Pathways ◽  
Protein Clearance ◽  
Multiple Processes

Age-associated neurodegenerative diseases are known to have “impaired protein clearance” as one of the key features causing their onset and progression. Hence, homeostasis is the key to maintaining balance throughout the cellular system as an organism ages. Any imbalance in the protein clearance machinery is responsible for accumulation of unwanted proteins, leading to pathological consequences—manifesting in neurodegeneration and associated debilitating outcomes. Multiple processes are involved in regulating this phenomenon; however, failure to regulate the autophagic machinery is a critical process that hampers the protein clearing pathway, leading to neurodegeneration. Another important and widely known component that plays a role in modulating neurodegeneration is a class of proteins called sirtuins. These are class III histone deacetylases (HDACs) that are known to regulate various vital processes such as longevity, genomic stability, transcription and DNA repair. These enzymes are also known to modulate neurodegeneration in an autophagy-dependent manner. Considering its genetic relevance and ease of studying disease-related endpoints in neurodegeneration, the model system Caenorhabditis elegans has been successfully employed in deciphering various functional outcomes related to critical protein molecules, cell death pathways and their association with ageing. This review summarizes the vital role of sirtuins and autophagy in ageing and neurodegeneration, in particular highlighting the knowledge obtained using the C. elegans model system.

scholarly journals Phase separation of proSAAS into spheres results in core sequestration of TDP-43216-414 aggregates

2020 ◽  
Author(s):  
Juan R. Peinado ◽  
Kriti Chaplot ◽  
Timothy S. Jarvela ◽  
Edward Barbieri ◽  
James Shorter ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Phase Separation ◽  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Model System ◽  
Chaperone Activity ◽  
Chaperone Proteins ◽  
Cytotoxic Effects ◽  
Vital Functions

SUMMARYChaperone proteins perform vital functions in the maintenance of cellular proteostasis and play important roles during the development of neurodegenerative diseases involving protein aggregation. We have previously reported that a secreted neuronal chaperone known as proSAAS exhibits potent chaperone activity in vitro against protein aggregation and blocks the cytotoxic effects of amyloid and α-synuclein oligomers. Here we report that overexpression of proSAAS generates dense, membraneless 2 μm spheres which can increase by fusion up to 4 μM during expression within the cytoplasm. The presence of dense proSAAS spheres was confirmed using electron microscopy. ProSAAS spheres selectively sequestered GFP-TDP-43216-414 within their cores, resulting in cellular redistribution and retardation of degradation. ProSAAS expression was protective against TDP-43 cytotoxicity in a yeast model system. Aggregate sequestration via proSAAS encapsulation may provide protection from cell-to-cell transmission of aggregates and explain the as-yet unclear mechanism underlying the cytoprotective chaperone action of proSAAS.

scholarly journals Yeast as a Model System to Study Tau Biology

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Ann De Vos ◽  
Jayamani Anandhakumar ◽  
Jeff Van den Brande ◽  
Mathias Verduyckt ◽  
Vanessa Franssens ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Neurodegenerative Diseases ◽  
Tau Phosphorylation ◽  
Model System ◽  
Human Protein ◽  
Protein Tau ◽  
Cellular Processes ◽  
Enormous Amount ◽  
Yeast Model

Hyperphosphorylated and aggregated human protein tau constitutes a hallmark of a multitude of neurodegenerative diseases called tauopathies, exemplified by Alzheimer's disease. In spite of an enormous amount of research performed on tau biology, several crucial questions concerning the mechanisms of tau toxicity remain unanswered. In this paper we will highlight some of the processes involved in tau biology and pathology, focusing on tau phosphorylation and the interplay with oxidative stress. In addition, we will introduce the development of a human tau-expressing yeast model, and discuss some crucial results obtained in this model, highlighting its potential in the elucidation of cellular processes leading to tau toxicity.

A Protozoan Model for Golgi-Associated Calcification

1971 ◽  
Vol 29 ◽  
pp. 332-333
Author(s):  
D. C. Williams ◽  
D. E. Outka
Keyword(s):  
Golgi Apparatus ◽  
Organic Matrix ◽  
Model System ◽  
Sequential Formation

Many studies have shown that the Golgi apparatus is involved in a variety of synthetic activities, and probably no Golgi product is more elaborate than the scales produced by various kinds of phytoflagellates. The formation of calcified scales (coccoliths, Fig. 1,2) of the coccolithophorid phytoflagellates provides a particularly interesting model system for the study of biological mineralization, and the sequential formation of Golgi products.The coccoliths of Hymenomonas carterae consist of a scale-like base (Fig. 2 and 4, b) with a highly structured calcified (CaCO3) rim composed of two distinct elements which alternate about the base periphery (Fig. 1 and 3, A, B). Each element is enveloped by a sheath-like organic matrix (Fig. 3; Fig. 4, m).

Existence of DNA in yeast microbodies

1978 ◽  
Vol 36 (2) ◽  
pp. 232-233
Author(s):  
Masako Osumi ◽  
Misuzu Nagano ◽  
Hiroko Kazama
Keyword(s):  
Catalase Activity ◽  
Buoyant Density ◽  
Model System ◽  
Contour Length ◽  
Native State ◽  
Normal Alkane ◽  
Remarkable Increase ◽  
Dna Molecule ◽  
Mitochondrial Dnas

We have found that microbodies appeared profusely together with a remarkable increase in catalase activity in normal alkane-grown cells of hydrocarbon-utilizing Candida yeasts, and that the microbodies multiplied by division in these cells. These features of Candida yeasts seem to provide a useful model system for studies on the biogenesis of the microbody. Subsequently, we have succeeded in isolation of Candida microbodies in an apparently native state, as judged biochemically and morphologically. The presence of DNA in the purified microbody fraction thus obtained was proved by the diphenylamine method. DNA molecule of about 15 urn in contour length was released from an isolated microbody. The physicochemical analyses of the microbody DNA revealed that its buoyant density differed from nuclear and mitochondrial DNAs. All these results lead us to the possibility that there is a novel type of DNA in microbodies.

The coprecipitation of Cr3P and Cr in Cu

1988 ◽  
Vol 46 ◽  
pp. 764-765
Author(s):  
M.J. Witcomb ◽  
U. Dahmen ◽  
K.H. Westmacott
Keyword(s):  
Orientation Relationship ◽  
Interface Structure ◽  
Model System ◽  
Relative Orientation ◽  
Age Hardening ◽  
Precipitation Behavior ◽  
Solution Treated ◽  
Small Needle ◽  
Diffraction Patterns ◽  
Interface Structures

Cu-Cr age-hardening alloys are of interest as a model system for the investigation of fcc/bcc interface structures. Several past studies have investigated the morphology and interface structure of Cr precipitates in a Cu matrix (1-3) and good success has been achieved in understanding the crystallography and strain contrast of small needle-shaped precipitates. The present study investigates the effect of small amounts of phosphorous on the precipitation behavior of Cu-Cr alloys.The same Cu-0.3% Cr alloy as was used in earlier work was rolled to a thickness of 150 μm, solution treated in vacuum at 1050°C for 1h followed by quenching and annealing for various times at 820 and 863°C.Two laths and their corresponding diffraction patterns in an alloy aged 2h at 820°C are shown in correct relative orientation in Fig. 1. To within the limit of accuracy of the diffraction patterns the orientation relationship was that of Kurdjumov-Sachs (KS), i.e. parallel close-packed planes and directions.

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