Selective neuronal vulnerability in Parkinson disease

Nature reviews. Neuroscience, Journal Year: 2017, Volume and Issue: 18(2), P. 101 - 113

Published: Jan. 20, 2017

Language: Английский

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Ultrasound Neuromodulation: A Review of Results, Mechanisms and Safety

Ultrasound in Medicine & Biology, Journal Year: 2019, Volume and Issue: 45(7), P. 1509 - 1536

Published: May 18, 2019

Ultrasonic neuromodulation is a rapidly growing field, in which low-intensity ultrasound (US) delivered to nervous system tissue, resulting transient modulation of neural activity. This review summarizes the findings central and peripheral systems from mechanistic studies cell culture cognitive behavioral humans. The mechanisms by US mechanically interacts with neurons could affect firing are presented. An in-depth safety assessment current shows that parameters for human fall within envelope imaging. Challenges associated accurately targeting monitoring response described. In conclusion, literature supports use as safe, non-invasive brain stimulation modality improved spatial localization depth compared alternative methods. neurostimulation has potential be used both scientific instrument investigate function therapeutic modulate

Language: Английский

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Phosphoregulated FMRP phase separation models activity-dependent translation through bidirectional control of mRNA granule formation

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(10), P. 4218 - 4227

Published: Feb. 14, 2019

Significance Activity-dependent translation, the reversible activation of translation in response to synaptic activity, is important for plasticity and long-term memory formation. How activity triggers silenced mRNAs within neuronal granules, which are membraneless RNA–protein assemblies, not clear. We show that C-terminal region Fragile X Mental Retardation Protein (FMRP), an abundant granule protein, phase separates vitro with RNA its separation fine-tuned by posttranslational modifications controlled neurons activity. observe correlated inhibition vitro, providing a conceptual framework unify FMRP’s diverse roles. Experimental bioinformatic data suggest may be general mechanism linked activity-dependent translation.

Language: Английский

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α-Synuclein binds to the ER–mitochondria tethering protein VAPB to disrupt Ca2+ homeostasis and mitochondrial ATP production

Acta Neuropathologica, Journal Year: 2017, Volume and Issue: 134(1), P. 129 - 149

Published: March 23, 2017

α-Synuclein is strongly linked to Parkinson's disease but the molecular targets for its toxicity are not fully clear. However, many neuronal functions damaged in regulated by signalling between endoplasmic reticulum (ER) and mitochondria. This involves close physical associations two organelles that mediated binding of integral ER protein vesicle-associated membrane protein-associated B (VAPB) outer mitochondrial protein, tyrosine phosphatase-interacting 51 (PTPIP51). VAPB PTPIP51 thus act as a scaffold tether organelles. Here we show α-synuclein binds overexpression wild-type familial mutant disrupt VAPB-PTPIP51 tethers loosen ER-mitochondria associations. disruption also seen neurons derived from induced pluripotent stem cells patients harbouring pathogenic triplication gene. We loosening contacts accompanied Ca2+ exchange ATP production. Such disruptions likely be particularly damaging heavily dependent on correct signaling ATP.

Language: Английский

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Altered calcium signaling in cancer cells

Biochimica et Biophysica Acta (BBA) - Biomembranes, Journal Year: 2014, Volume and Issue: 1848(10), P. 2502 - 2511

Published: Aug. 20, 2014

Language: Английский

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Calcium signaling and molecular mechanisms underlying neurodegenerative diseases

Cell Calcium, Journal Year: 2017, Volume and Issue: 70, P. 87 - 94

Published: June 30, 2017

Language: Английский

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CB1 Receptor Signaling in the Brain: Extracting Specificity from Ubiquity

Neuropsychopharmacology, Journal Year: 2017, Volume and Issue: 43(1), P. 4 - 20

Published: Sept. 1, 2017

Endocannabinoids (eCBs) are amongst the most ubiquitous signaling molecules in nervous system. Over past few decades, observations based on a large volume of work, first examining pharmacological effects exogenous cannabinoids, and then physiological functions eCBs, have directly challenged long-held dogmatic views about communication, plasticity behavior central system (CNS). The eCBs their cognate cannabinoid receptors exhibit number unique properties that distinguish them from widely studied classical amino-acid transmitters, neuropeptides, catecholamines. Although we now loose set mechanistic rules experimental findings, new studies continue to reveal our understanding eCB (ECS) is continuously evolving challenging conventions. Here will briefly summarize findings current canonical view ‘ECS’ address novel aspects how nearly can determine highly specific brain. In particular, focus push for an expansion ideas around beliefs that, while clearly true, may be contributing oversimplified perspective at microscopic level impacts macroscopic level.

Language: Английский

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Apoptosis regulation in the penumbra after ischemic stroke: expression of pro- and antiapoptotic proteins

APOPTOSIS, Journal Year: 2019, Volume and Issue: 24(9-10), P. 687 - 702

Published: June 29, 2019

Language: Английский

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Mitochondrial dynamics in neuronal injury, development and plasticity

Journal of Cell Science, Journal Year: 2017, Volume and Issue: 130(4), P. 671 - 681

Published: Feb. 3, 2017

Mitochondria fulfill numerous cellular functions including ATP production, Ca2+ buffering, neurotransmitter synthesis and degradation, ROS production sequestration, apoptosis intermediate metabolism. Mitochondrial dynamics, a collective term for the processes of mitochondrial fission, fusion transport, governs function localization within cell. Correct balance dynamics is especially important in neurons as mutations fission enzymes cause peripheral neuropathies impaired development nervous system humans. Regulation partly accomplished through post-translational modification enzymes, turn influencing bioenergetics transport. The importance regulation highlighted by neurodegenerative disorders associated with enzyme Drp1. Not surprisingly, also play an physiological role synaptic plasticity. Here, we highlight recent findings underlying mechanisms relation to neurological disease, well plasticity system.

Language: Английский

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Alzheimer’s Disease: From Firing Instability to Homeostasis Network Collapse

Neuron, Journal Year: 2018, Volume and Issue: 97(1), P. 32 - 58

Published: Jan. 1, 2018

Language: Английский

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