Expression of NALP1 in cerebellar granule neurons stimulates apoptosis

Liu, Feng; Lo, Cody; Ning, Xiaoping; Kajkowski, Eileen M.; Jin, Mei; Chiriac, Camelia; Gonzales, Cathleen; Naureckiene, Saule; Lock, Yeung-Wai; Pong, Kevin; Zaleska, Margaret M.; Jacobsen, J. Steven; Silverman, Sanford J.; Ozenberger, Bradley A.

doi:10.1016/j.cellsig.2004.02.006

Cited by 30 publications

(21 citation statements)

References 30 publications

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“…For example, the NLRP3 inflammasome is mainly expressed in immune cells in the CNS, whereas the NLRP1 inflammasome is mainly expressed in neurons. [62][63][64][65] However, induction of both, NLRP1 and NLRP3 inflammasomes in ischemic neurons during stroke has been shown. 4 Making it more complex, certain human and murine inflammasome subunits differ substantially in their structure: in contrast to human NLRP1 inflammasome, murine NLRP1 is devoid of a PYD domain, which is thought to be essential to bind the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) to activate caspase-1.…”

Section: Inflammasome: Intracellular Sensor For Danger Signals and Ismentioning

confidence: 99%

Molecular Regulation of Cell Fate in Cerebral Ischemia: Role of the Inflammasome and Connected Pathways

Trendelenburg

2014

J Cereb Blood Flow Metab

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Analogous to Toll-like receptors, NOD-like receptors represent a class of pattern recognition receptors, which are cytosolic and constitute part of different inflammasomes. These large protein complexes are activated not only by different pathogens, but also by sterile inflammation or by specific metabolic conditions. Mutations can cause hereditary autoinflammatory systemic diseases, and inflammasome activation has been linked to many multifactorial diseases, such as diabetes or cardiovascular diseases. Increasing data also support an important role in different central nervous diseases such as stroke. Thus, the current knowledge of the functional role of this intracellular 'master switch' of inflammation is discussed with a focus on its role in ischemic stroke, neurodegeneration, and also with regard to the recent data which argues for a relevant role in other organs or biologic systems which influence stroke incidence or prognosis.

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Section: Inflammasome: Intracellular Sensor For Danger Signals and Ismentioning

confidence: 99%

Molecular Regulation of Cell Fate in Cerebral Ischemia: Role of the Inflammasome and Connected Pathways

Trendelenburg

2014

J Cereb Blood Flow Metab

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“…Studies have shown that the cerebellum is one of these areas. There are reports in the literature demonstrating that apoptosis is one of the mechanisms triggered in the cerebellum during focal cerebral ischemia 6 . Associated with cerebral ischemia, many harmful agents are studied.…”

Section: Introductionmentioning

confidence: 99%

Morphological and immunohistochemical analysis of apoptosis in the cerebellum of rats subjected to focal cerebral ischemia with or without alcoholism model

Carvalho

Tirapelli²,

Rodrigues³

et al. 2016

Acta Cir. Bras.

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Brazil. Conception, design, intellectual and scientific content of the study; manuscript writing, critical revision; supervision of all phases of the study. ABSTRACT PURPOSE:To evaluated histopathological changes, morphometric and expression of proteins CASPASE-3, BCL-2 and XIAP related to apoptosis in the cerebellum after induction of temporary focal cerebral ischemia followed by reperfusion, with or without a model of chronic alcoholism. METHODS:Fifty Wistar rats were used and divided into: control group (C), sham group (S), ischemic group (I), alcoholic group (A), and ischemic and alcoholic group (IA). The cerebellum samples collected were stained for histopathological and morphometric analysis and immunohistochemistry study. RESULTS:Histopathological changes were observed a greater degree in animals in groups A and IA. The morphometric study showed no difference in the amount of cells in the granular layer of the cerebellum between the groups. The expression of CASPASE-3 was higher than BCL-2 and XIAP in the groups A and IA. CONCLUSION:We observed correlation between histopathological changes and the occurrence of apoptosis in cerebellar cortex.

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“…Rat cerebellar granule neurons submitted to oxygen and glucose deprivation or reduced potassium levels increased Nlrp1 mRNA levels. 25,26 Nuclear Nlrp1 or functional Nlrp1 inflammasome complexes increased in rat cortical neurons after traumatic brain injury, stroke, and glucose-oxygen deprivation insults. [27][28][29][30][31] Neuronal Nlrp1 increased in rats submitted to spinal cord or sciatic nerve injury, 29,32 and in aging rat hippocampus or ethanol treated hippocampal slice cultures.…”

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confidence: 99%

Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation

et al. 2015

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Neuronal active Caspase-6 (Casp6) is associated with Alzheimer disease (AD), cognitive impairment, and axonal degeneration. Caspase-1 (Casp1) can activate Casp6 but the expression and functionality of Casp1-activating inflammasomes has not been welldefined in human neurons. Here, we show that primary cultures of human CNS neurons expressed functional Nod-like receptor protein 1 (NLRP1), absent in melanoma 2, and ICE protease activating factor, but not the NLRP3, inflammasome receptor components. NLRP1 neutralizing antibodies in a cell-free system, and NLRP1 siRNAs in neurons hampered stress-induced Casp1 activation. NLRP1 and Casp1 siRNAs also abolished stress-induced Casp6 activation in neurons. The functionality of the NLRP1 inflammasome in serum-deprived neurons was also demonstrated by NLRP1 siRNA-mediated inhibition of speck formation of the apoptosis-associated speck-like protein containing a caspase recruitment domain conjugated to green fluorescent protein. These results indicated a novel stress-induced intraneuronal NLRP1/Casp1/Casp6 pathway. Lipopolysaccharide induced Casp1 and Casp6 activation in wild-type mice brain cortex, but not in that of Nlrp1 − / − and Casp1 − / − mice. NLRP1 immunopositive neurons were increased 25-to 30-fold in AD brains compared with non-AD brains. NLRP1 immunoreactivity in these neurons co-localized with Casp6 activity. Furthermore, the NLRP1/Casp1/Casp6 pathway increased amyloid beta peptide 42 ratio in serum-deprived neurons. Therefore, CNS human neurons express functional NLRP1 inflammasomes, which activate Casp1 and subsequently Casp6, thus revealing a fundamental mechanism linking intraneuronal inflammasome activation to Casp1-generated interleukin-1-β-mediated neuroinflammation and Casp6-mediated axonal degeneration.

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Expression of NALP1 in cerebellar granule neurons stimulates apoptosis

Cited by 30 publications

References 30 publications

Molecular Regulation of Cell Fate in Cerebral Ischemia: Role of the Inflammasome and Connected Pathways

Molecular Regulation of Cell Fate in Cerebral Ischemia: Role of the Inflammasome and Connected Pathways

Morphological and immunohistochemical analysis of apoptosis in the cerebellum of rats subjected to focal cerebral ischemia with or without alcoholism model

Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation

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