Microtubule affinity regulating kinase 4: A potential drug target from cancers to neurodegenerative diseases

Annadurai, Narendran; Das, Viswanath

doi:10.1016/b978-0-323-91287-7.00017-x

Cited by 3 publications

(6 citation statements)

References 127 publications

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“…In this article, the structure and relative area of another 10 metabolites that appeared in all three populations isolated in different habitats are described. Some of the metabolites are known, found in various organisms in the animal kingdom, whereas for others, the information is limited to type, i.e., steroidal alkaloids [10]. In most cases, the structure has been described in online databases such as the National Center for Biotechnology Information (NCBI).…”

Section: Discussionmentioning

confidence: 99%

“…Nebrosteroid L, a 19-oxygenated steroid, has been evaluated for its anti-inflammatory activity in RAW 264.7 macrophages [9]. Cholic acid is an amphiphilic steroidal molecule which, along with chenodeoxycholic acid, is a major bile acid produced by the liver, where it is synthesized from cholesterol; cholic acid is used to treat bile acid synthesis disorder because it suppresses the production of toxic bile acid intermediates [10]. 5α-Dihydronandrolone (also known as 5α-DHN, dihydronandrolone, DHN, 5α-dihydro-19-nortestosterone, or 5α-estran-17β-ol-3-one) is a naturally occurring anabolic-androgenic steroid and a 5α-reduced derivative of nandrolone (19-nortestosterone); it is a major metabolite of nandrolone.…”

Section: Introductionmentioning

confidence: 99%

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Skin Mucus Metabolites in Salamandra Infraimmaculata from Various Habitats

Degani,

Peretz,

Musa

2023

Endocrinol Metab Nutr

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We conducted an untargeted metabolomics analysis of the skin mucus of Near Eastern fire salamanders (Salamandra infraimmaculata) using LC-MS/MS. Samples were collected from salamanders living in three distinct locations along the southern border of their distribution in Israel: Kibbutz Sasa in the Upper Galilee and Manof in the Lower Galilee, both semi-arid mountainous regions, and Dan River, which has a constant year-round water supply with stable temperature. We identified and described 10 metabolites found in the mucus of S. infraimmaculata in all three habitats. These substances belong to various chemical groups, and we provide their chemical structures and secretion levels. Salamanders from Dan had a greater number of metabolites (5 out of 10) at higher concentrations compared to the Manof and Sasa populations. In addition, differences were observed in 6 mucus metabolites among the mountain populations. Findings support the hypothesis that the extreme habitat conditions in the southern range influence the quantity and composition of salamander mucus secretions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Skin Mucus Metabolites in Salamandra Infraimmaculata from Various Habitats

Degani,

Peretz,

Musa

2023

Endocrinol Metab Nutr

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“…Other advantages include prolonged pharmacodynamics, high potency, and the capability for validating pharmacological specificity via mutation of the reactive cysteine residue. 17 Key oncogenic kinase drug targets activate important cancer cell pathways and are linked to the mutations in phosphatase. 68 Mutations in protein kinase genes are frequently associated with tumor initiation and its progression.…”

Section: Mark4 Mutationsmentioning

confidence: 99%

“…Several signaling pathways engaged with multiple disorders are also shown. This figure was adapted from Anwar et al 12 and Annadurai and Das 17 . MARK4, microtubule‐affinity regulating kinase 4.…”

Section: Introductionmentioning

confidence: 99%

“…Mutation in signaling pathways leads to several diseases, including cancer and AD. Other advantages include prolonged pharmacodynamics, high potency, and the capability for validating pharmacological specificity via mutation of the reactive cysteine residue 17 . Key oncogenic kinase drug targets activate important cancer cell pathways and are linked to the mutations in phosphatase 68 .…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic targeting of microtubule affinity‐regulating kinase 4 in cancer and neurodegenerative diseases

Alam,

Ahmed,

Abid

et al. 2023

J of Cellular Biochemistry

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Microtubule affinity‐regulating kinase 4 (MARK4) is a member of the Ser/Thr protein kinase family, phosphorylates the microtubule‐connected proteins and plays a vital role in causing cancers and neurodegenerative diseases. This kinase modulates multiple signaling pathways, including mammalian target of rapamycin, nuclear factor‐κB, and Hippo‐signaling, presumably responsible for cancer and Alzheimer's. MARK4 acts as a negative controller of the Hippo‐kinase cassette for promoting YAP/TAZ action, and the loss of MARK4 detains the tumorigenic properties of cancer cells. MARK4 is involved in tau hyperphosphorylation that consequently affects neurodegeneration. MARK4 is a promising drug target for cancer, diabetes, and Alzheimer's. Developing the potent and selective inhibitors of MAKR4 are promising in the therapeutic management of associated diseases. Despite its great significance, a few reviews are available to discuss its structure, function and clinical significance. In the current review, we aimed to provide detailed information on the structural features of MARK4 targeted in drug development and its role in various signaling pathways related to cancer and neurodegenerative diseases. We further described the therapeutic potential of MARK4 inhibitors in preventing numerous diseases. Finally, the updated information on MARK4 will be helpful in the further development of effective therapeutic molecules.

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Antineoplastics for treating Alzheimer's disease and dementia: Evidence from preclinical and observational studies

Das,

Miller,

Alladi

et al. 2024

Medicinal Research Reviews

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As the world population ages, there will be an increasing need for effective therapies for aging‐associated neurodegenerative disorders, which remain untreatable. Dementia due to Alzheimer's disease (AD) is one of the leading neurological diseases in the aging population. Current therapeutic approaches to treat this disorder are solely symptomatic, making the need for new molecular entities acting on the causes of the disease extremely urgent. One of the potential solutions is to use compounds that are already in the market. The structures have known pharmacokinetics, pharmacodynamics, toxicity profiles, and patient data available in several countries. Several drugs have been used successfully to treat diseases different from their original purposes, such as autoimmunity and peripheral inflammation. Herein, we divulge the repurposing of drugs in the area of neurodegenerative diseases, focusing on the therapeutic potential of antineoplastics to treat dementia due to AD and dementia. We briefly touch upon the shared pathological mechanism between AD and cancer and drug repurposing strategies, with a focus on artificial intelligence. Next, we bring out the current status of research on the development of drugs, provide supporting evidence from retrospective, clinical, and preclinical studies on antineoplastic use, and bring in new areas, such as repurposing drugs for the prion‐like spreading of pathologies in treating AD.

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Microtubule affinity regulating kinase 4: A potential drug target from cancers to neurodegenerative diseases

Cited by 3 publications

References 127 publications

Skin Mucus Metabolites in Salamandra Infraimmaculata from Various Habitats

Skin Mucus Metabolites in Salamandra Infraimmaculata from Various Habitats

Therapeutic targeting of microtubule affinity‐regulating kinase 4 in cancer and neurodegenerative diseases

Antineoplastics for treating Alzheimer's disease and dementia: Evidence from preclinical and observational studies

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