NF1 tumor suppressor in epidermal wound healing with special focus on wound healing in patients with type 1 neurofibromatosis

: Diabetes is a chronic metabolic disorder of endocrine system characterized by increase in blood glucose level. Several factors such as pancreatic damage, oxidative stress, infection, genetic factor, obesity, liver dysfunction play a vital role in pathogenesis of diabetes which further lead to serious diabetic complications. Diabetic wound is one such complication where the wound formation occurs, especially due to pressure and its healing process is disrupted due to factors such as hyperglycemia, neuropathy, nephropathy, peripheral vascular disease, reduction of blood flow, atherosclerosis, impaired fibroblast. Process of wound healing is delayed due to different abnormalities like alteration in nitric oxide level, increase in aldose reductase, sorbitol and fructose. Therefore, diabetic wound requires more time to heal as compare to normal wound. Healing time is delayed in diabetic wound due to many factors such as stress, decreased oxygenation supply, infection, decreased blood flow, impaired proliferation and migration rate, impaired growth factor production, impaired keratinocytes proliferation and migration, and altered vascular endothelial mediators. The current treatment for diabetic wound includes wound patches, oxygenation therapy, hydrogel patches, gene therapy, laser therapy, and stem cell therapy. Medications with phytoconstituents is also one way to manage diabetic wound, but it is not more effective for quick healing. The objective of this review is to understand the potential of various management options which are available for diabetic wound, with a special focus on biological cells.

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Merlin cooperates with neurofibromin and Spred1 to suppress the Ras–Erk pathway

Human Molecular Genetics ◽

10.1093/hmg/ddaa263 ◽

2020 ◽

Author(s):

Yan Cui ◽

Lin Ma ◽

Stephan Schacke ◽

Jiani C Yin ◽

Yi-Ping Hsueh ◽

...

Keyword(s):

Tumor Suppressor ◽

Binding Sites ◽

Neurofibromatosis Type ◽

Kinase Domain ◽

Erk Pathway ◽

Suppressor Activity ◽

The Third ◽

Tumor Suppressor Activity ◽

Multiple Signaling

Abstract The Ras–Erk pathway is frequently over-activated in human tumors. Neurofibromatosis type 1 and 2 (NF1, NF2) are characterized by multiple tumors of Schwann cell origin. The NF1 tumor suppressor neurofibromin is a principal Ras-GAP accelerating Ras inactivation, whereas the NF2 tumor suppressor merlin is a scaffold protein coordinating multiple signaling pathways. We have previously reported that merlin interacts with Ras and p120RasGAP. Here, we show that merlin can also interact with the neurofibromin/Spred1 complex via merlin-binding sites present on both proteins. Further, merlin can directly bind to the Ras-binding domain and the kinase domain of Raf1. As the third component of the neurofibromin/Spred1 complex, merlin cannot increase the Ras-GAP activity; rather, it blocks Ras binding to Raf1 by functioning as a ‘selective Ras barrier’. Merlin-deficient Schwann cells require the Ras–Erk pathway activity for proliferation. Accordingly, suppression of the Ras–Erk pathway likely contributes to merlin’s tumor suppressor activity. Taken together, our results, and studies by others, support targeting or co-targeting of this pathway as a therapy for NF2 inactivation-related tumors.

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Multifunctional hydrogels for wound healing: Special focus on biomacromolecular based hydrogels

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2020.12.202 ◽

2020 ◽

Author(s):

Nahideh Asadi ◽

Hamidreza Pazoki-Toroudi ◽

Azizeh Rahmani Del Bakhshayesh ◽

Abolfazl Akbarzadeh ◽

Soodabeh Davaran ◽

...

Keyword(s):

Wound Healing ◽

Special Focus

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A rare case of cervical hypoglossal nerve neurofibromas in a patient with type 1 neurofibromatosis

Brazilian Journal of Otorhinolaryngology ◽

10.1016/j.bjorl.2021.01.006 ◽

2021 ◽

Author(s):

Sai-Guan Lum ◽

Marina Mat Baki ◽

Mohd Razif Mohamad Yunus

Keyword(s):

Rare Case ◽

Hypoglossal Nerve ◽

Type 1 Neurofibromatosis

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Nutraceuticals for Wound Healing: A Special Focus on Chromolaena odorata as Guardian of Health with Broad Spectrum of Biological Activities

Nutraceuticals in Veterinary Medicine ◽

10.1007/978-3-030-04624-8_36 ◽

2019 ◽

pp. 541-562

Author(s):

Mohamed Ali-Seyed ◽

Kavitha Vijayaraghavan

Keyword(s):

Wound Healing ◽

Broad Spectrum ◽

Biological Activities ◽

Special Focus ◽

Chromolaena Odorata

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Type 1 neurofibromatosis and pulmonary hypertension: a report of two cases and a review

Heart Asia ◽

10.1136/heartasia-2012-010093 ◽

2012 ◽

Vol 4 (1) ◽

pp. 27-30 ◽

Cited By ~ 3

Author(s):

Amit Malviya ◽

Sundeep Mishra ◽

Shyam S Kothari

Keyword(s):

Pulmonary Hypertension ◽

Type 1 Neurofibromatosis

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Neurofibromin can inhibit Ras-dependent growth by a mechanism independent of its GTPase-accelerating function

Molecular and Cellular Biology ◽

10.1128/mcb.14.1.641-645.1994 ◽

1994 ◽

Vol 14 (1) ◽

pp. 641-645

Author(s):

M R Johnson ◽

J E DeClue ◽

S Felzmann ◽

W C Vass ◽

G Xu ◽

...

Keyword(s):

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Suppressor Gene ◽

Protein Product ◽

Growth Inhibitory ◽

Nf1 Gene ◽

A Cell ◽

Dependent Growth ◽

Nih 3T3

The NF1 gene, which is altered in patients with type 1 neurofibromatosis, has been postulated to function as a tumor suppressor gene. The NF1 protein product neurofibromin stimulates the intrinsic GTPase activity of active GTP-bound Ras, thereby inactivating it. Consistent with a tumor suppressor function, we have found that the introduction of NF1 in melanoma cell lines that are deficient in neurofibromin inhibited their growth and induced their differentiation. In addition, overexpression of neurofibromin in NIH 3T3 cells was growth inhibitory but did not alter the level of GTP.Ras in the cells. Transformation by v-ras, whose protein product is resistant to GTPase stimulation by neurofibromin, was inhibited in a cell line overexpressing neurofibromin, while transformation by v-raf was not altered. The results demonstrate that NF1 is a tumor suppressor gene that can inhibit Ras-dependent growth by a regulatory mechanism that is independent of neurofibromin's ability to stimulate Ras GTPase.

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MEN4 and CDKN1B mutations: the latest of the MEN syndromes

Endocrine Related Cancer ◽

10.1530/erc-17-0243 ◽

2017 ◽

Vol 24 (10) ◽

pp. T195-T208 ◽

Cited By ~ 52

Author(s):

Rami Alrezk ◽

Fady Hannah-Shmouni ◽

Constantine A Stratakis

Keyword(s):

Tumor Suppressor ◽

Neuroendocrine Tumors ◽

Pituitary Adenomas ◽

Wide Spectrum ◽

Susceptibility Gene ◽

Germline Mutations ◽

Suppressor Gene ◽

Loss Of Function ◽

Putative Tumor Suppressor

Multiple endocrine neoplasia (MEN) refers to a group of autosomal dominant disorders with generally high penetrance that lead to the development of a wide spectrum of endocrine and non-endocrine manifestations. The most frequent among these conditions is MEN type 1 (MEN1), which is caused by germline heterozygous loss-of-function mutations in the tumor suppressor geneMEN1. MEN1 is characterized by primary hyperparathyroidism (PHPT) and functional or nonfunctional pancreatic neuroendocrine tumors and pituitary adenomas. Approximately 10% of patients with familial or sporadic MEN1-like phenotype do not haveMEN1mutations or deletions. A novel MEN syndrome was discovered, initially in rats (MENX), and later in humans (MEN4), which is caused by germline mutations in the putative tumor suppressorCDKN1B. The most common phenotype of the 19 established cases of MEN4 that have been described to date is PHPT followed by pituitary adenomas. Recently, somatic or germline mutations inCDKN1Bwere also identified in patients with sporadic PHPT, small intestinal neuroendocrine tumors, lymphoma and breast cancer, demonstrating a novel role forCDKN1Bas a tumor susceptibility gene for other neoplasms. In this review, we report on the genetic characterization and clinical features of MEN4.

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