keyword
MENU ▼
Read by QxMD icon Read
search

Sarm1

keyword
https://www.readbyqxmd.com/read/28683272/axon-death-pathways-converge-on-axundead-to-promote-functional-and-structural-axon-disassembly
#1
Lukas J Neukomm, Thomas C Burdett, Andrew M Seeds, Stefanie Hampel, Jaeda C Coutinho-Budd, Jonathan E Farley, Jack Wong, Yonca B Karadeniz, Jeannette M Osterloh, Amy E Sheehan, Marc R Freeman
Axon degeneration is a hallmark of neurodegenerative disease and neural injury. Axotomy activates an intrinsic pro-degenerative axon death signaling cascade involving loss of the NAD(+) biosynthetic enzyme Nmnat/Nmnat2 in axons, activation of dSarm/Sarm1, and subsequent Sarm-dependent depletion of NAD(+). Here we identify Axundead (Axed) as a mediator of axon death. axed mutants suppress axon death in several types of axons for the lifespan of the fly and block the pro-degenerative effects of activated dSarm in vivo...
July 5, 2017: Neuron
https://www.readbyqxmd.com/read/28630328/toll-like-receptor-pathway-evolution-in-deuterostomes
#2
Michael G Tassia, Nathan V Whelan, Kenneth M Halanych
Animals have evolved an array of pattern-recognition receptor families essential for recognizing conserved molecular motifs characteristic of pathogenic microbes. One such family is the Toll-like receptors (TLRs). On pathogen binding, TLRs initiate specialized cytokine signaling catered to the class of invading pathogen. This signaling is pivotal for activating adaptive immunity in vertebrates, suggesting a close evolutionary relationship between innate and adaptive immune systems. Despite significant advances toward understanding TLR-facilitated immunity in vertebrates, knowledge of TLR pathway evolution in other deuterostomes is limited...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28559111/pattern-recognition-receptors-in-grass-carp-ctenopharyngodon-idella-i-organization-and-expression-analysis-of-tlrs-and-rlrs
#3
Zhiwei Liao, Quanyuan Wan, Hang Su, Changsong Wu, Jianguo Su
Pattern recognition receptors (PRRs) play indispensable roles in the immune responses against invading pathogens. In the present study, we systematically identified and characterized Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) as well as their adaptors in grass carp (Ctenopharyngodon idella). A comprehensive analysis of BLAST and other bioinformatics methods showed that C. idella TLR family consist of 21 members and their adaptors contain four members. Phylogenetic analyses confirmed the existence of six TLR subfamilies (TLR1, 3, 4, 5, 7 and 11 subfamily) in C...
May 27, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28485482/deletion-of-sarm1-gene-is-neuroprotective-in-two-models-of-peripheral-neuropathy
#4
Elliot Turkiew, Debbie Falconer, Nicole Reed, Ahmet Höke
Distal axon degeneration seen in many peripheral neuropathies is likely to share common molecular mechanisms with Wallerian degeneration. Although several studies in mouse models of peripheral neuropathy showed prevention of axon degeneration in the slow Wallerian degeneration (Wlds) mouse, the role of a recently identified player in Wallerian degeneration, Sarm1, has not been explored extensively. In this study, we show that mice lacking the Sarm1 gene are resistant to distal axonal degeneration in a model of chemotherapy induced peripheral neuropathy caused by paclitaxel and a model of high fat diet induced putative metabolic neuropathy...
September 2017: Journal of the Peripheral Nervous System: JPNS
https://www.readbyqxmd.com/read/28447196/the-axon-degeneration-gene-sarm1-is-evolutionarily-distinct-from-other-tir-domain-containing-proteins
#5
Harsha Malapati, Spencer M Millen, William J Buchser
Many forms of neurodegenerative disease are characterized by Wallerian degeneration, an active program of axonal destruction. Recently, the important player which enacts Wallerian degeneration was discovered, the multidomain protein SARM1. Since the SARM1 protein has classically been thought of as an innate immune molecule, its role in Wallerian degeneration has raised questions on the evolutionary forces acting on it. Here, we synthesize a picture of SARM1's evolution through various organisms by examining the molecular and genetic changes of SARM1 and the genes around it...
August 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28334607/the-sarm1-toll-interleukin-1-receptor-domain-possesses-intrinsic-nad-cleavage-activity-that-promotes-pathological-axonal-degeneration
#6
Kow Essuman, Daniel W Summers, Yo Sasaki, Xianrong Mao, Aaron DiAntonio, Jeffrey Milbrandt
Axonal degeneration is an early and prominent feature of many neurological disorders. SARM1 is the central executioner of the axonal degeneration pathway that culminates in depletion of axonal NAD(+), yet the identity of the underlying NAD(+)-depleting enzyme(s) is unknown. Here, in a series of experiments using purified proteins from mammalian cells, bacteria, and a cell-free protein translation system, we show that the SARM1-TIR domain itself has intrinsic NADase activity-cleaving NAD(+) into ADP-ribose (ADPR), cyclic ADPR, and nicotinamide, with nicotinamide serving as a feedback inhibitor of the enzyme...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28334598/tir-axons-apart-unpredicted-nadase-controls-axonal-degeneration
#7
Ron Goldner, Avraham Yaron
SARM1 is a key regulator of axonal degeneration. However, SARM1 mechanism of action is not clear. In this issue of Neuron, Essuman et al. (2017) reveal an intrinsic NADase activity in the SARM1-TIR domain that is required for axonal degeneration.
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28285993/death-receptor-6-promotes-wallerian-degeneration-in-peripheral-axons
#8
Kanchana K Gamage, Irene Cheng, Rachel E Park, Mardeen S Karim, Kazusa Edamura, Christopher Hughes, Anthony J Spano, Alev Erisir, Christopher D Deppmann
Axon degeneration during development is required to sculpt a functional nervous system and is also a hallmark of pathological insult, such as injury [1, 2]. Despite similar morphological characteristics, very little overlap in molecular mechanisms has been reported between pathological and developmental degeneration [3-5]. In the peripheral nervous system (PNS), developmental axon pruning relies on receptor-mediated extrinsic degeneration mechanisms to determine which axons are maintained or degenerated [5-7]...
March 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28095293/mapk-signaling-promotes-axonal-degeneration-by-speeding-the-turnover-of-the-axonal-maintenance-factor-nmnat2
#9
Lauren J Walker, Daniel W Summers, Yo Sasaki, E J Brace, Jeffrey Milbrandt, Aaron DiAntonio
Injury-induced (Wallerian) axonal degeneration is regulated via the opposing actions of pro-degenerative factors such as SARM1 and a MAPK signal and pro-survival factors, the most important of which is the NAD(+) biosynthetic enzyme NMNAT2 that inhibits activation of the SARM1 pathway. Here we investigate the mechanism by which MAPK signaling facilitates axonal degeneration. We show that MAPK signaling promotes the turnover of the axonal survival factor NMNAT2 in cultured mammalian neurons as well as the Drosophila ortholog dNMNAT in motoneurons...
January 17, 2017: ELife
https://www.readbyqxmd.com/read/27797810/prevention-of-vincristine-induced-peripheral-neuropathy-by-genetic-deletion-of-sarm1-in-mice
#10
Stefanie Geisler, Ryan A Doan, Amy Strickland, Xin Huang, Jeffrey Milbrandt, Aaron DiAntonio
Peripheral polyneuropathy is a common and dose-limiting side effect of many important chemotherapeutic agents. Most such neuropathies are characterized by early axonal degeneration, yet therapies that inhibit this axonal destruction process do not currently exist. Recently, we and others discovered that genetic deletion of SARM1 (sterile alpha and TIR motif containing protein 1) dramatically protects axons from degeneration after axotomy in mice. This finding fuels hope that inhibition of SARM1 or its downstream components can be used therapeutically in patients threatened by axonal loss...
December 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27735788/nmnat1-inhibits-axon-degeneration-via-blockade-of-sarm1-mediated-nad-depletion
#11
Yo Sasaki, Takashi Nakagawa, Xianrong Mao, Aaron DiAntonio, Jeffrey Milbrandt
Overexpression of the NAD(+) biosynthetic enzyme NMNAT1 leads to preservation of injured axons. While increased NAD(+) or decreased NMN levels are thought to be critical to this process, the mechanism(s) of this axon protection remain obscure. Using steady-state and flux analysis of NAD(+) metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD(+) synthesis, NMNAT1 instead blocks the injury-induced, SARM1-dependent NAD(+) consumption that is central to axon degeneration...
October 13, 2016: ELife
https://www.readbyqxmd.com/read/27671644/sarm1-specific-motifs-in-the-tir-domain-enable-nad-loss-and-regulate-injury-induced-sarm1-activation
#12
Daniel W Summers, Daniel A Gibson, Aaron DiAntonio, Jeffrey Milbrandt
Axon injury in response to trauma or disease stimulates a self-destruction program that promotes the localized clearance of damaged axon segments. Sterile alpha and Toll/interleukin receptor (TIR) motif-containing protein 1 (SARM1) is an evolutionarily conserved executioner of this degeneration cascade, also known as Wallerian degeneration; however, the mechanism of SARM1-dependent neuronal destruction is still obscure. SARM1 possesses a TIR domain that is necessary for SARM1 activity. In other proteins, dimerized TIR domains serve as scaffolds for innate immune signaling...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27197022/axon-degeneration-context-defines-distinct-pathways
#13
REVIEW
Matthew J Geden, Mohanish Deshmukh
Axon degeneration is an essential part of development, plasticity, and injury response and has been primarily studied in mammalian models in three contexts: 1) Axotomy-induced Wallerian degeneration, 2) Apoptosis-induced axon degeneration (axon apoptosis), and 3) Axon pruning. These three contexts dictate engagement of distinct pathways for axon degeneration. Recent advances have identified the importance of SARM1, NMNATs, NAD+ depletion, and MAPK signaling in axotomy-induced Wallerian degeneration. Interestingly, apoptosis-induced axon degeneration and axon pruning have many shared mechanisms both in signaling (e...
August 2016: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/27062141/molecular-mechanisms-in-the-initiation-phase-of-wallerian-degeneration
#14
REVIEW
Biao Chang, Qi Quan, Shibi Lu, Yu Wang, Jiang Peng
Axonal degeneration is an early hallmark of nerve injury and many neurodegenerative diseases. The discovery of the Wallerian degeneration slow mutant mouse, in which axonal degeneration is delayed, revealed that Wallerian degeneration is an active progress and thereby illuminated the mechanisms underlying axonal degeneration. Nicotinamide mononucleotide adenylyltransferase 2 and sterile alpha and armadillo motif-containing protein 1 play essential roles in the maintenance of axon integrity by regulating the level of nicotinamide adenine dinucleotide, which seems to be the key molecule involved in the maintenance of axonal health...
August 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/26912636/attenuated-traumatic-axonal-injury-and-improved-functional-outcome-after-traumatic-brain-injury-in-mice-lacking-sarm1
#15
Nils Henninger, James Bouley, Elif M Sikoglu, Jiyan An, Constance M Moore, Jean A King, Robert Bowser, Marc R Freeman, Robert H Brown
Axonal degeneration is a critical, early event in many acute and chronic neurological disorders. It has been consistently observed after traumatic brain injury, but whether axon degeneration is a driver of traumatic brain injury remains unclear. Molecular pathways underlying the pathology of traumatic brain injury have not been defined, and there is no efficacious treatment for traumatic brain injury. Here we show that mice lacking the mouse Toll receptor adaptor Sarm1 (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) gene, a key mediator of Wallerian degeneration, demonstrate multiple improved traumatic brain injury-associated phenotypes after injury in a closed-head mild traumatic brain injury model...
April 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/26844829/axon-self-destruction-new-links-among-sarm1-mapks-and-nad-metabolism
#16
REVIEW
Josiah Gerdts, Daniel W Summers, Jeffrey Milbrandt, Aaron DiAntonio
Wallerian axon degeneration is a form of programmed subcellular death that promotes axon breakdown in disease and injury. Active degeneration requires SARM1 and MAP kinases, including DLK, while the NAD+ synthetic enzyme NMNAT2 prevents degeneration. New studies reveal that these pathways cooperate in a locally mediated axon destruction program, with NAD+ metabolism playing a central role. Here, we review the biology of Wallerian-type axon degeneration and discuss the most recent findings, with special emphasis on critical signaling events and their potential as therapeutic targets for axonopathy...
February 3, 2016: Neuron
https://www.readbyqxmd.com/read/26820848/axonal-transport-and-secretion-of-fibrillar-forms-of-%C3%AE-synuclein-a%C3%AE-42-peptide-and-httexon-1
#17
Michel Brahic, Luc Bousset, Gregor Bieri, Ronald Melki, Aaron D Gitler
Accruing evidence suggests that prion-like behavior of fibrillar forms of α-synuclein, β-amyloid peptide and mutant huntingtin are responsible for the spread of the lesions that characterize Parkinson disease, Alzheimer disease and Huntington disease, respectively. It is unknown whether these distinct protein assemblies are transported within and between neurons by similar or distinct mechanisms. It is also unclear if neuronal death or injury is required for neuron-to-neuron transfer. To address these questions, we used mouse primary cortical neurons grown in microfluidic devices to measure the amounts of α-synuclein, Aβ42 and HTTExon1 fibrils transported by axons in both directions (anterograde and retrograde), as well as to examine the mechanism of their release from axons after anterograde transport...
April 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/26686637/wallerian-degeneration-is-executed-by-an-nmn-sarm1-dependent-late-ca-2-influx-but-only-modestly-influenced-by-mitochondria
#18
Andrea Loreto, Michele Di Stefano, Martin Gering, Laura Conforti
Axon injury leads to rapid depletion of NAD-biosynthetic enzyme NMNAT2 and high levels of its substrate, NMN. We proposed a key role for NMN in Wallerian degeneration but downstream events and their relationship to other mediators remain unclear. Here, we show, in vitro and in vivo, that axotomy leads to a late increase in intra-axonal Ca(2+), abolished by pharmacological or genetic reduction of NMN levels. NMN requires the pro-degenerative protein SARM1 to stimulate Ca(2+) influx and axon degeneration. While inhibition of NMN synthesis and SARM1 deletion block Ca(2+) rise and preserve axonal integrity, they fail to prevent early mitochondrial dynamic changes...
December 22, 2015: Cell Reports
https://www.readbyqxmd.com/read/26423149/sarm1-not-myd88-mediates-tlr7-tlr9-induced-apoptosis-in-neurons
#19
Piyali Mukherjee, Clayton W Winkler, Katherine G Taylor, Tyson A Woods, Vinod Nair, Burhan A Khan, Karin E Peterson
Neuronal apoptosis is a key aspect of many different neurologic diseases, but the mechanisms remain unresolved. Recent studies have suggested a mechanism of innate immune-induced neuronal apoptosis through the stimulation of endosomal TLRs in neurons. TLRs are stimulated both by pathogen-associated molecular patterns as well as by damage-associated molecular patterns, including microRNAs released by damaged neurons. In the present study, we identified the mechanism responsible for TLR7/TLR9-mediated neuronal apoptosis...
November 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/26059317/neurodegeneration-in-c-elegans-models-of-als-requires-tir-1-sarm1-immune-pathway-activation-in-neurons
#20
Julie Vérièpe, Lucresse Fossouo, J Alex Parker
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease thought to employ cell non-autonomous mechanisms where neuronal injury engages immune responses to influence disease progression. Here we show that the expression of mutant proteins causative for ALS in Caenorhabditis elegans motor neurons induces an innate immune response via TIR-1/Sarm1. Loss of function mutations in tir-1, associated downstream kinases, and the transcription factor atf-7 all suppress motor neuron degeneration. The neurosecretory proteins UNC-13 and UNC-31 are required for induction of the immune response as well as the degeneration of motor neurons...
2015: Nature Communications
keyword
keyword
53069
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"