scholarly journals Proteoglycan-Mediated Axon Degeneration Corrects Pretarget Topographic Sorting Errors

Neuron ◽  
2013 ◽  
Vol 78 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Fabienne E. Poulain ◽  
Chi-Bin Chien
Keyword(s):  
Axon Degeneration

Axon degeneration: Mechanisms and implications of a distinct program from cell death

2010 ◽  
Vol 56 (4) ◽  
pp. 529-534 ◽  
Author(s):  
Tingting Yan ◽  
Yan Feng ◽  
Qiwei Zhai
Keyword(s):  
Cell Death ◽  
Axon Degeneration

scholarly journals Molecular analysis of axonal-intrinsic and glial-associated co-regulation of axon degeneration

2017 ◽  
Vol 8 (11) ◽  
pp. e3166-e3166 ◽  
Author(s):  
Alejandra Catenaccio ◽  
Maica Llavero Hurtado ◽  
Paula Diaz ◽  
Douglas J Lamont ◽  
Thomas M Wishart ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Axon Degeneration

Role of the Akt/GSK-3β/CRMP-2 pathway in axon degeneration of dopaminergic neurons resulting from MPP+ toxicity

2015 ◽  
Vol 1602 ◽  
pp. 9-19 ◽  
Author(s):  
Wei Fang ◽  
Guodong Gao ◽  
Haikang Zhao ◽  
Yi Xia ◽  
Xiaodong Guo ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Axon Degeneration ◽  
Gsk 3Β

scholarly journals TMEM184B promotes pruriceptive neuron specification to allow itch sensitivity

2020 ◽  
Author(s):  
Erik G. Larsen ◽  
Tiffany S. Cho ◽  
Matthew L. McBride ◽  
Jing Feng ◽  
Bhagyashree Manivannan ◽  
...  
Keyword(s):  
Dorsal Root ◽  
Somatosensory System ◽  
Lineage Tracing ◽  
Mutant Mice ◽  
Axon Degeneration ◽  
Leukotriene C4 ◽  
Drg Neurons ◽  
Early Failure ◽  
Neuronal Subtype ◽  
Signaling Components

AbstractNociceptive and pruriceptive neurons in the dorsal root ganglia (DRG) convey sensations of pain and itch to the spinal cord, respectively. One subtype of mature DRG neurons, marked by Somatostatin (Sst) expression, is responsible for sensing mediators of acute itch and atopic dermatitis, including the cytokine IL-31. How itch-sensitive (pruriceptive) neurons are specified is unclear. Here we show that Tmem184b, a gene with roles in axon degeneration and nerve terminal maintenance, is required for the expression of a large cohort of itch receptors, including those for IL-31, Leukotriene C4, and Histamine. Mice lacking Tmem184b fail to respond to IL-31, but maintain normal responses to pain and mechanical force, indicating a specific behavioral defect in pruriception. Lineage-tracing studies using Sst-driven Cre recombinase show a loss of pruriceptive neurons in Tmem184b-mutant mice, suggesting a defect in neuron subtype specification. We identify an early failure of proper Wnt-dependent transcriptional signatures and signaling components in Tmem184b mutant mice that can explain the improper DRG neuronal subtype specification. Lentiviral re-expression of Tmem184b in mutant embryonic neurons restores Wnt signatures, whereas re-expression of Tmem184b in adult DRG fails to restore itch responses. Together, these data demonstrate that Tmem184b promotes adult somatosensation through developmental Wnt signaling and specification of pruriceptive neurons. Our data illuminate a new key regulatory step in the processes controlling the establishment of diversity in the somatosensory system.

scholarly journals Nicotinic acid mononucleotide is an allosteric SARM1 inhibitor promoting axonal protection

2021 ◽  
Author(s):  
Yo Sasaki ◽  
Jian Zhu ◽  
Yun Shi ◽  
Weixi Gu ◽  
Bostjan Kobe ◽  
...  
Keyword(s):  
Nicotinic Acid ◽  
Neurodegenerative Disorders ◽  
Axon Degeneration ◽  
Biosynthetic Enzyme ◽  
Allosteric Site ◽  
Nicotinamide Mononucleotide ◽  
Bacterial Enzyme ◽  
Axon Loss ◽  
Metabolic Sensor

SARM1 is an inducible NAD+ hydrolase that is the central executioner of pathological axon loss. Recently, we elucidated the molecular mechanism of SARM1 activation, demonstrating that SARM1 is a metabolic sensor regulated by the levels of NAD+ and its precursor, nicotinamide mononucleotide (NMN), via their competitive binding to an allosteric site. In healthy neurons with abundant NAD+, binding of NAD+ blocks access of NMN to this allosteric site. However, with injury or disease the levels of the NAD+ biosynthetic enzyme NMNAT2 drop, increasing the NMN/NAD+ ratio and thereby promoting NMN binding to the SARM1 allosteric site, which in turn induces a conformational change activating the SARM1 NAD+ hydrolase. Hence, NAD+ metabolites both regulate the activation of SARM1 and, in turn, are regulated by the SARM1 NAD+ hydrolase. This dual upstream and downstream role for NAD+ metabolites in SARM1 function has hindered mechanistic understanding of axoprotective mechanisms that manipulate the NAD+ metabolome. Here we reevaluate two methods that potently block axon degeneration via modulation of NAD+ related metabolites, 1) the administration of the NMN biosynthesis inhibitor FK866 in conjunction with the NAD+ precursor nicotinic acid riboside (NaR) and 2) the neuronal expression of the bacterial enzyme NMN deamidase. We find that these approaches not only lead to a decrease in the levels of the SARM1 activator NMN, but also an increase in the levels of the NAD+ precursor nicotinic acid mononucleotide (NaMN). We show that NaMN competes with NMN for binding to the SARM1 allosteric site, that NaMN inhibits SARM1 activation, and that this NaMN-mediated inhibition is important for the long-term axon protection induced by these treatments. Together, these results demonstrate that the SARM1 allosteric pocket can bind a diverse set of metabolites including NMN, NAD+, and NaMN to monitor cellular NAD+ homeostasis and regulate SARM1 NAD+ hydrolase activity. The relative promiscuity of the allosteric site may enable the development of potent pharmacological inhibitors of SARM1 activation for the treatment of neurodegenerative disorders.

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