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Familial Hyperparathyroidism
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Luigia Cinque, Alfredo Scillitani, Vito Guarnieri
As part of the human PAF1 complex that binds at the residues 223–415, parafibromin is required for expression of several cellular genes involved in cell cycle regulation, cell growth, protein synthesis, and lipid and nucleic acid metabolism. The protein has multiple functions, including (i) behind the regulation of genetic transcription, parafibromin interacts with the histone methyltransferase complex for histone modifications and chromatin remodeling [75,80]; (ii) it regulates cell growth via the (iii) downregulation of cyclin D1 expression and Wnt signaling [81,82] and (iv) inhibition of the c-myc proto-oncogene [83,84].
Isolation, Fractionation, and Analysis of Nonhistone Chromosomal Proteins
Published in Lubomir S. Hnilica, Chromosomal Nonhistone Proteins, 2018
Leokadia Klyszejko-Stefanowicz, Lubomir S. Hnilica
Chromatin, the interphase chromosomal material of eukaryotic cells is a complex of DNA with a fixed level of histone proteins, variable amounts of nonhistone chromosomal proteins (NHCP), and small amounts of RNA. Of these principal chromatin components, the nonhistone proteins have received considerable attention as a class of macromolecules which may be associated with the regulation of genetic transcription.1–4,25
The Primer Hypothesis for the Regulation of Eukaryotic Gene Expression
Published in M. Gerald, M.D. Kolodny, Eukaryotic Gene Regulation, 2018
Other evidence for the ability of cytoplasmic factors to activate genetic transcription has been described. Harris86 found that when the fully differentiated avian erythrocyte with a completely repressed genome was transplanted into a HeLa cell, the nucleus began to swell and to synthesize RNA. Possibly, the cytoplasmic factors involved were RNA molecules activating transcription in the transplanted nucleus. Other studies, utilizing transplantation of nuclei from one species or one stage of development to another, have shown the decisive influence of cytoplasmic factors on differentiation in development. These studies have been reviewed in amoeba,87 amphibia,88 and insects.89It is certainly possible that the cytoplasmic factors involved are primer RNA segments.
Neuroprotective effect of standardized extracts of three Lactuca sativa Linn. varieties against 3-NP induced Huntington’s disease like symptoms in rats
Published in Nutritional Neuroscience, 2022
Jai Malik, Supreet Kaur, Maninder Karan, Sunayna Choudhary
Huntington’s disease (HD) is a fatal genetic autosomal-dominant neuro-disorder causing progressive neuronal damage. It is characterized by progressive motor dysfunction including dyskinesia, chorea (brief irregular and involuntary movements), dystonia, weight loss, deterioration of memory, and other associated CNS disorders like anxiety, depression, etc.1 Altered genetic transcription (results from an unstable expansion of a CAG (cytosine-adenine-guanine) trinucleotide repeat in the HTT (huntingtin) gene), oxidative stress, glutamate excitotoxicity and mitochondrial dysfunction are considered as the mainstay in the pathophysiology of the disorder leading to neurodegeneration.2 Today, lots of emphasis is given on proper diet and its role in delaying the onset of various degenerative disorders especially neurodegenerative disorders.3 Mediterranean diet, and diet rich in polyphenols have shown to slow the disease progression, an increase in survival rate, lowers the comorbidity and motor impairment, and improves the overall quality of life in patients suffering from HD4 and other neurodegenerative disorders.5
Strategies for targeting undruggable targets
Published in Expert Opinion on Drug Discovery, 2022
Gong Zhang, Juan Zhang, Yuting Gao, Yangfeng Li, Yizhou Li
For undruggable targets, another stunning approach is manipulating at genetic/transcription level rather than protein level. Small interfering RNA (siRNA) down-regulates mRNA and subsequent protein expression[46]. There have been over 50 siRNA-based clinical trials, including attempts to target mutant-specific p53 to treat kidney acute renal failure by I5NP (QPI-1002) and silence c-myc to treat solid tumor or multiple myeloma[47]. CRISPR-Cas technology is also a promising gene-editing strategy for future therapeutics (Figure 1e)[48]. These strategies are still faced with challenges, to name a few, delivery efficiency, rapid degradation, and off-target effect. These limitations might be solved by chemical modification, rational sequence design, and exquisite RNA carrier system. RNA-based therapies could be complementary to the strategies above on the therapeutic entity level to synergistically crack undruggable targets.
A patent review of BRD4 inhibitors (2013-2019)
Published in Expert Opinion on Therapeutic Patents, 2020
Tian Lu, Wenchao Lu, Cheng Luo
Acetylation of lysine residues on histone tails is one of the primary epigenetic modifications. The bromodomain (BRD) is the first protein binding domain known to be able to specifically recognize the acetylated lysine mark. BRDs play an important role in the genetic transcription of chromatin due to their unique recognition for acetylated lysine (KAc) [1–4]. Studies indicate that the occurrence and development of many tumors are closely related to BRD4 dysfunction [5,6]. Thus, BRD4 has been considered as an attractive candidate target for the treatment of different types of cancers [7,8]. So far, numerous chemical scaffolds of BRD4 have been developed and show great anti-tumor effect in a variety of tumors [9]. The present paper reviews newly patented BRD4 inhibitors from 2013 to 2019, summarizes its structure, molecular mechanism of action, pharmacological activity and potential clinical applications.