Abstract：
:SARM is the fifth and most conserved member of the Toll/Il-1 Receptor (TIR) adaptor family. However, unlike the other TIR adaptors, MyD88, Mal, TRIF and TRAM, SARM does not participate in transducing signals downstream of TLRs. By contrast SARM inhibits TLR signalling by interacting with the adaptors TRIF and MyD88. In addition, SARM also has positive roles in innate immunity by activating specific transcriptional programs following immune challenge. SARM has a pivotal role in activating different forms of cell death following cellular stress and viral infection. Many of these functions of mammalian SARM are also reflected in SARM orthologues in lower organisms such as C. elegans and Drosophila. SARM expression is particularly enriched in neurons of the CNS and SARM has a critical role in neuronal death and in axon degeneration. Recent fascinating molecular insights have been revealed as to the molecular mechanism of SARM mediated axon degeneration. SARM has been shown to deplete NAD+ by possessing intrinsic NADase activity in the TIR domain of the protein. This activity can be activated experimentally by forced dimerization of the TIR domain. It is thought that this activity of SARM is normally switched off by the axo-protective activities of NMNAT2 which maintain low levels of the NAD+ precursor NMN. Therefore, there is now great excitement in the field of SARM research as targeting this enzymatic activity of SARM may lead to the development of new therapies for neurodegenerative diseases such as multiple sclerosis and motor neuron disease.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Carty M,Bowie AGdoi
10.1016/j.bcp.2019.01.005subject
Has Abstractpub_date
2019-03-01 00:00:00pages
52-62eissn
0006-2952issn
1873-2968pii
S0006-2952(19)30011-5journal_volume
161pub_type
杂志文章,评审abstract：:The characterization of the potent p38 inhibitor BIRB796 as a dual inhibitor of p38/Jun N-terminal kinases (JNK) mitogen-activated protein kinases (EC 2.7.11.24) has complicated the interpretation of its reported anti-inflammatory activity. To better understand the contribution of JNK2 inhibition to the anti-inflammat...
journal_title：Biochemical pharmacology
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journal_title：Biochemical pharmacology
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
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doi：10.1016/0006-2952(90)90349-p
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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pub_type： 杂志文章
doi：10.1016/0006-2952(85)90560-x
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pub_type： 杂志文章
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pub_type： 杂志文章
doi：10.1016/j.bcp.2006.06.003
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01385-0
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：1986-10-01 00:00:00
