scholarly journals Proteomic Techniques to Examine Neuronal Translational Dynamics

2019 ◽  
Vol 20 (14) ◽  
pp. 3524 ◽  
Author(s):  
Shon A. Koren ◽  
Drew A. Gillett ◽  
Simon V. D’Alton ◽  
Matthew J. Hamm ◽  
Jose F. Abisambra
Keyword(s):  
Quantitative Analysis ◽  
Neurodegenerative Diseases ◽  
Behavioral Outcomes ◽  
Spatiotemporal Dynamics ◽  
Mammalian Brain ◽  
Short Timescale ◽  
Ribosomal Function ◽  
Recent Developments ◽  
Proteomic Techniques

Impairments in translation have been increasingly implicated in the pathogenesis and progression of multiple neurodegenerative diseases. Assessing the spatiotemporal dynamics of translation in the context of disease is a major challenge. Recent developments in proteomic analyses have enabled the resolution of nascent peptides in a short timescale on the order of minutes. In addition, a quantitative analysis of translation has progressed in vivo, showing remarkable potential for coupling these techniques with cognitive and behavioral outcomes. Here, we review these modern approaches to measure changes in translation and ribosomal function with a specific focus on current applications in the mammalian brain and in the study of neurodegenerative diseases.

scholarly journals In vivo imaging of injured cortical axons reveals a rapid onset form of Wallerian degeneration

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Alison Jane Canty ◽  
Johanna Sara Jackson ◽  
Lieven Huang ◽  
Antonio Trabalza ◽  
Cher Bass ◽  
...  
Keyword(s):  
Nervous System ◽  
Wallerian Degeneration ◽  
Molecular Mechanisms ◽  
Rapid Onset ◽  
Spatiotemporal Dynamics ◽  
Myelinated Fibre ◽  
Mammalian Brain ◽  
Axon Loss ◽  
Synaptic Mechanisms

Abstract Background Despite the widespread occurrence of axon and synaptic loss in the injured and diseased nervous system, the cellular and molecular mechanisms of these key degenerative processes remain incompletely understood. Wallerian degeneration (WD) is a tightly regulated form of axon loss after injury, which has been intensively studied in large myelinated fibre tracts of the spinal cord, optic nerve and peripheral nervous system (PNS). Fewer studies, however, have focused on WD in the complex neuronal circuits of the mammalian brain, and these were mainly based on conventional endpoint histological methods. Post-mortem analysis, however, cannot capture the exact sequence of events nor can it evaluate the influence of elaborated arborisation and synaptic architecture on the degeneration process, due to the non-synchronous and variable nature of WD across individual axons. Results To gain a comprehensive picture of the spatiotemporal dynamics and synaptic mechanisms of WD in the nervous system, we identify the factors that regulate WD within the mouse cerebral cortex. We combined single-axon-resolution multiphoton imaging with laser microsurgery through a cranial window and a fluorescent membrane reporter. Longitudinal imaging of > 150 individually injured excitatory cortical axons revealed a threshold length below which injured axons consistently underwent a rapid-onset form of WD (roWD). roWD started on average 20 times earlier and was executed 3 times slower than WD described in other regions of the nervous system. Cortical axon WD and roWD were dependent on synaptic density, but independent of axon complexity. Finally, pharmacological and genetic manipulations showed that a nicotinamide adenine dinucleotide (NAD+)-dependent pathway could delay cortical roWD independent of transcription in the damaged neurons, demonstrating further conservation of the molecular mechanisms controlling WD in different areas of the mammalian nervous system. Conclusions Our data illustrate how in vivo time-lapse imaging can provide new insights into the spatiotemporal dynamics and synaptic mechanisms of axon loss and assess therapeutic interventions in the injured mammalian brain.

Peptides and their Metal Complexes in Neurodegenerative Diseases: from Structural Studies to Nanomedicine Prospects

2018 ◽  
Vol 25 (6) ◽  
pp. 715-747 ◽  
Author(s):  
Giuseppe Trapani ◽  
Cristina Satriano ◽  
Diego La Mendola
Keyword(s):  
Neurodegenerative Diseases ◽  
Metal Ions ◽  
Metal Binding ◽  
Crucial Role ◽  
Neuronal Development ◽  
Protein Complexes ◽  
Specific Binding ◽  
Biological Properties ◽  
Recent Developments

Background: The metal ions dyshomeostasis is increasingly recognized to play a crucial role in the development of aging-related neurodegenerative diseases. Metal trafficking in the brain is related to proteins regulating both uptake and efflux of metals in neurons. Different pathways may occur, depending on specific binding features of metallo-protein complexes. In particular, copper, zinc and iron are recognized to influence the biochemistry of proteins involved in neurodegeneration (for instance Aβ and α-synuclein), as well as those playing a crucial role in neuronal development and efficiency (neurotrophins). Nowadays the application of peptide-based drugs is widespread for different pathologies, but the short lifetime in vivo due to proteolysis and other shortcomings still limit their use. Methods: A structured search was performed about the state of the art on: i) peptidomimetic approaches used to obtain peptides mimicking the metal binding activities of proteins involved in neurons survival, ii) peptide-based nanostructures, as promising biomaterials in tissue engineering and substrates for neurites outgrowth and synapses formation. Results: Recent developments on metal-binding peptides and peptide nanostructures for therapeutic application in neurodegenerative diseases are reviewed, showing as metal ions interaction may affect structural and biological properties of different proteins involved in neurodegenerative diseases. Conclusion: This review provides a survey on peptides able to mimic some biofunctional activities of the whole protein, e.g., the binding features to metal ions, thus highlighting their promising potentialities as new, more effective, therapeutics. The integration of such peptides into multifunctional nanoplatforms can be a smart route for the development of biomaterials scaffolds and nanomedicine applications.

scholarly journals The Emerging Use ofIn VivoOptical Imaging in the Study of Neurodegenerative Diseases

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Aileen P. Patterson ◽  
Stephanie A. Booth ◽  
Reuben Saba
Keyword(s):  
Neurodegenerative Diseases ◽  
Optical Imaging ◽  
Neuronal Damage ◽  
Mammalian Brain ◽  
Reporter Mice ◽  
Highly Sensitive ◽  
Charged Couple Device ◽  
Living Tissues ◽  
Lateral Sclerosis

The detection and subsequent quantification of photons emitted from living tissues, using highly sensitive charged-couple device (CCD) cameras, have enabled investigators to noninvasively examine the intricate dynamics of molecular reactions in wide assortment of experimental animals under basal and pathophysiological conditions. Nevertheless, extrapolation of thisin vivooptical imaging technology to the study of the mammalian brain and related neurodegenerative conditions is still in its infancy. In this review, we introduce the reader to the emerging use ofin vivooptical imaging in the study of neurodegenerative diseases. We highlight the current instrumentation that is available and reporter molecules (fluorescent and bioluminescent) that are commonly used. Moreover, we examine howin vivooptical imaging using transgenic reporter mice has provided new insights into Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Prion disease, and neuronal damage arising from excitotoxicity and inflammation. Furthermore, we also touch upon studies that have utilized these technologies for the development of therapeutic strategies for neurodegenerative conditions that afflict humans.

Solving the mechanisms responsible for organelle behavior in vivo by same-cell correlative light and electron microscopy

1992 ◽  
Vol 50 (1) ◽  
pp. 14-15
Author(s):  
Conly L. Rieder
Keyword(s):  
Electron Microscopy ◽  
Quantitative Analysis ◽  
Light Microscopy ◽  
Living Cell ◽  
Light And Electron Microscopy ◽  
Time Behavior ◽  
Dynamic Interactions ◽  
Positive Identification ◽  
Cellular Components

The behavior of many cellular components, and their dynamic interactions, can be characterized in the living cell with considerable spatial and temporal resolution by video-enhanced light microscopy (video-LM). Indeed, under the appropriate conditions video-LM can be used to determine the real-time behavior of organelles ≤ 25-nm in diameter (e.g., individual microtubules—see). However, when pushed to its limit the structures and components observed within the cell by video-LM cannot be resolved nor necessarily even identified, only detected. Positive identification and a quantitative analysis often requires the corresponding electron microcopy (EM).

Potential for Treatment of Neurodegenerative Diseases with Natural Products or Synthetic Compounds that Stabilize Microtubules

2020 ◽  
Vol 26 (35) ◽  
pp. 4362-4372
Author(s):  
John H. Miller ◽  
Viswanath Das
Keyword(s):  
Natural Products ◽  
Neurodegenerative Diseases ◽  
In Vivo Models ◽  
Synthetic Compounds ◽  
Stabilizing Agents ◽  
Animal Models Of Disease ◽  
Model Studies ◽  
Models Of Disease

No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, or Pick’s disease. A number of in vitro and in vivo models exist for studying neurodegenerative diseases, including cell models employing induced-pluripotent stem cells, cerebral organoids, and animal models of disease. Recent research has focused on microtubulestabilizing agents, either natural products or synthetic compounds that can prevent the axonal destruction caused by tau protein pathologies. Although promising results have come from animal model studies using brainpenetrant natural product microtubule-stabilizing agents, such as paclitaxel analogs that can access the brain, epothilones B and D, and other synthetic compounds such as davunetide or the triazolopyrimidines, early clinical trials in humans have been disappointing. This review aims to summarize the research that has been carried out in this area and discuss the potential for the future development of an effective microtubule stabilizing drug to treat neurodegenerative disease.

Neurochemistry of L-Glutamate Transport in the CNS: A Review of Thirty Years of Progress

2001 ◽  
Vol 66 (9) ◽  
pp. 1315-1340 ◽  
Author(s):  
Vladimir J. Balcar ◽  
Akiko Takamoto ◽  
Yukio Yoneda
Keyword(s):  
Molecular Biology ◽  
Glutamate Transport ◽  
Mammalian Brain ◽  
Activity Data ◽  
System A ◽  
Recent Developments ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Disease Analysis

The review highlights the landmark studies leading from the discovery and initial characterization of the Na+-dependent "high affinity" uptake in the mammalian brain to the cloning of individual transporters and the subsequent expansion of the field into the realm of molecular biology. When the data and hypotheses from 1970's are confronted with the recent developments in the field, we can conclude that the suggestions made nearly thirty years ago were essentially correct: the uptake, mediated by an active transport into neurons and glial cells, serves to control the extracellular concentrations of L-glutamate and prevents the neurotoxicity. The modern techniques of molecular biology may have provided additional data on the nature and location of the transporters but the classical neurochemical approach, using structural analogues of glutamate designed as specific inhibitors or substrates for glutamate transport, has been crucial for the investigations of particular roles that glutamate transport might play in health and disease. Analysis of recent structure/activity data presented in this review has yielded a novel insight into the pharmacological characteristics of L-glutamate transport, suggesting existence of additional heterogeneity in the system, beyond that so far discovered by molecular genetics. More compounds that specifically interact with individual glutamate transporters are urgently needed for more detailed investigations of neurochemical characteristics of glutamatergic transport and its integration into the glutamatergic synapses in the central nervous system. A review with 162 references.

scholarly journals Persistent luminescence nanoparticles for cancer theranostics application

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Nian Liu ◽  
Xiao Chen ◽  
Xia Sun ◽  
Xiaolian Sun ◽  
Junpeng Shi
Keyword(s):  
Uv Light ◽  
Combined Therapy ◽  
Tumor Therapy ◽  
High Sensitivity ◽  
Persistent Luminescence ◽  
Therapeutic Drugs ◽  
High Penetration ◽  
Recent Developments ◽  
Cancer Theranostics

AbstractPersistent luminescence nanoparticles (PLNPs) are unique optical materials that emit afterglow luminescence after ceasing excitation. They exhibit unexpected advantages for in vivo optical imaging of tumors, such as autofluorescence-free, high sensitivity, high penetration depth, and multiple excitation sources (UV light, LED, NIR laser, X-ray, and radiopharmaceuticals). Besides, by incorporating other functional molecules, such as photosensitizers, photothermal agents, or therapeutic drugs, PLNPs are also widely used in persistent luminescence (PersL) imaging-guided tumor therapy. In this review, we first summarize the recent developments in the synthesis and surface functionalization of PLNPs, as well as their toxicity studies. We then discuss the in vivo PersL imaging and multimodal imaging from different excitation sources. Furthermore, we highlight PLNPs-based cancer theranostics applications, such as fluorescence-guided surgery, photothermal therapy, photodynamic therapy, drug/gene delivery and combined therapy. Finally, future prospects and challenges of PLNPs in the research of translational medicine are also discussed.

scholarly journals Effect of Antioxidant Therapy on Oxidative Stress In Vivo

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 344
Author(s):  
Anna Maria Fratta Pasini ◽  
Luciano Cominacini
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Neurodegenerative Diseases ◽  
Antioxidant Therapy ◽  
Potential Benefits

Over the last few decades, many efforts have been put into fields that explore the potential benefits of antioxidants, especially with regards to aging, cancer, cardiovascular diseases, and neurodegenerative diseases. [...]

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