Last update 19 Sep 2024

MAP3K13

Last update 19 Sep 2024

Basic Info

Synonyms

Leucine zipper-bearing kinase, LZK, MAP3K13

+ [4]

Introduction

Activates the JUN N-terminal pathway through activation of the MAP kinase kinase MAP2K7. Acts synergistically with PRDX3 to regulate the activation of NF-kappa-B in the cytosol. This activation is kinase-dependent and involves activating the IKK complex, the IKBKB-containing complex that phosphorylates inhibitors of NF-kappa-B.

Drugs associated with MAP3K13

DN-1289

Target

MAP3K12 x MAP3K13

Mechanism

MAP3K12 inhibitors [+1]

Active Org.

Denali Therapeutics, Inc.

Originator Org.

Denali Therapeutics, Inc.

Active Indication

Amyotrophic Lateral Sclerosis [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with MAP3K13

100 Translational Medicine associated with MAP3K13

0 Patents (Medical) associated with MAP3K13

169

Literatures (Medical) associated with MAP3K13

01 May 2024·Ear, Nose & Throat JournalQ4 · MEDICINE

Head and Neck Malignant Paragangliomas: Experience from a Single Institution

Q4 · MEDICINE

ArticleOA

Author: Han, Demin ; Ding, Yiming ; Chen, Xiaohong ; Wang, Shaozhong ; Li, Lifeng

Objectives: To summarize the clinicopathological and genetic features of malignant paragangliomas in head and neck cancer and to explore the appropriate treatment options for this rare lesion. Methods: Six patients harboring head and neck malignant paraganglioma from Beijing Tongren Hospital were retrospectively reviewed. The clinicopathological characteristics, gene mutations, and prognosis of these patients were analyzed. Results: Of these 6 patients, 3 were male and 3 were female; 4 patients harbored malignant carotid body tumors, and two had malignant vagal paragangliomas. Three patients had cervical lymph node metastasis, two presented with lung and bone metastasis, and 1 had lung and liver metastasis. Of the 6 patients, four underwent surgical resection, and the other two patients denied surgery and instead received chemotherapy with paclitaxel, ifosfamide, and dacarbazine. These 2 patients with vagal paraganglioma received postoperative radiotherapy. All 6 patients are still alive at the present time, with a median follow-up time of 66 months. Positive Ki-67 expression in tumor tissue ranged from 1% to 40%. Genetic mutations in SDHD, SDHB, ATR, and MAP3K13 were identified in 4 patients. Conclusions: After comprehensive treatment, head and neck malignant paraganglioma can attain a favorable prognosis. Genetic mutations are commonly detected in patients with malignant paragangliomas. This study also identified mutations in ATR and MAP3K13 in these patients.

01 Apr 2024·International Journal of Pediatric Otorhinolaryngology

Correlation of patient reported outcome measures with endoscopic findings in pediatric chronic adenoiditis and chronic rhinosinusitis

Article

Author: Ramadan, Hassan H ; McArdle, Erica ; Makary, Chadi A ; Shetty, Sameer ; Coutinho, Dominic

BACKGROUNDStudies in adult chronic rhinosinusitis (CRS) showed poor correlation between patient reported outcome measures (PROMs) and objective findings. Our goal is to study the correlation between the sinus and nasal quality of life (SN-5) and the 22-items sinonasal outcome test (SNOT-22) surveys with endoscopy findings in children with chronic adenoiditis (CA) and CRS.METHODSCross-sectional study of all pediatric patients (age 2-18) presenting for CA or CRS was performed. Patients and caregivers were asked to fill the SN-5 and SNOT-22 questionnaires at initial and follow up visits. Demographics and comorbidities were collected. Objective findings included endoscopy Modified Lund-Kennedy (MLK) scores and adenoid tissue size.RESULTS124 children were included, with mean age of 9.9 years (SD = 4.8) and 46.8% female. 36.3% had allergic rhinitis, 23.4% had asthma, and 4% had obstructive sleep apnea. Moderate correlation was found between the rhinologic domain of SNOT-22 and MLK scores (r = 0.36, p = 0.001) and between SN5 scores and adenoid size in all patients (r = 0.39, p < 0.001). SNOT-22 scores showed moderate correlation with adenoid size (r = 0.42, p < 0.001) more specifically in CA patients (r = 0.54, p < 0.001). The correlation of SN5 and MLK scores were higher in children with allergic rhinitis or asthma. The correlation between SN5 and adenoid size was lower in children with allergic rhinitis or asthma.CONCLUSIONThere is discrepancy between the subjective measures and the objective findings in children with CA or CRS. The physical exam findings may not reflect the effect of CRS on the quality of life of children.

01 Aug 2023·Journal of Neurotrauma

Traumatic Axonal Injury in the Optic Nerve: The Selective Role of SARM1 in the Evolution of Distal Axonopathy

Article

Author: Lehar, Mohamed ; Alexandris, Athanasios S. ; Welsbie, Derek ; Perdomo, Dianela ; Zack, Donald J. ; Koliatsos, Vassilis E. ; Alam, Zahra ; McKenney, James ; Ryu, Jiwon ; Lee, Youngrim

Traumatic axonal injury (TAI), thought to be caused by rotational acceleration of the head, is a prevalent neuropathology in traumatic brain injury (TBI). TAI in the optic nerve is a common finding in multiple blunt-force TBI models and hence a great model to study mechanisms and treatments for TAI, especially in view of the compartmentalized anatomy of the visual system. We have previously shown that the somata and the proximal, but not distal, axons of retinal ganglion cells (RGC) respond to DLK/LZK blockade after impact acceleration of the head (IA-TBI). Here, we explored the role of the sterile alpha and TIR-motif containing 1 (SARM1), the key driver of Wallerian degeneration (WD), in the progressive breakdown of distal and proximal segments of the optic nerve following IA-TBI with high-resolution morphological and classical neuropathological approaches. Wild type and Sarm1 knockout (KO) mice received IA-TBI or sham injury and were allowed to survive for 3, 7, 14, and 21 days. Ultrastructural and microscopic analyses revealed that TAI in the optic nerve is characterized by variable involvement of individual axons, ranging from apparent early disconnection of a subpopulation of axons to a range of ongoing axonal and myelin perturbations. Traumatic axonal injury resulted in the degeneration of a population of axons distal and proximal to the injury, along with retrograde death of a subpopulation of RGCs. Quantitative analyses on proximal and distal axons and RGC somata revealed that different neuronal domains exhibit differential vulnerability, with distal axon segments showing more severe degeneration compared with proximal segments and RGC somata. Importantly, we found that Sarm1 KO had a profound effect in the distal optic nerve by suppressing axonal degeneration by up to 50% in the first 2 weeks after IA-TBI, with a continued but lower effect at 3 weeks, while also suppressing microglial activation. Sarm1 KO had no evident effect on the initial traumatic disconnection and did not ameliorate the proximal optic axonopathy or the subsequent attrition of RGCs, indicating that the fate of different axonal segments in the course of TAI may depend on distinct molecular programs within axons.

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MAP3K13

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