scholarly journals Pharmacological Findings on the Biochemical Bases of Memory Processes: A General View

2004 ◽  
Vol 11 (3-4) ◽  
pp. 159-189 ◽  
Author(s):  
Iván Izquierdo ◽  
Martín Cammarota ◽  
Jorge H. Medina ◽  
Lia R. M. Bevilaqua
Keyword(s):  
Mental Disorders ◽  
Molecular Mechanisms ◽  
Brain Structures ◽  
Fear Memory ◽  
Brain Regions ◽  
General View ◽  
Therapeutic Approaches ◽  
The Past ◽  
New Therapeutic Approaches ◽  
Pharmacological Studies

We have advanced considerably in the past 2 to 3 years in understanding the molecular mechanisms of consolidation, retrieval, and extinction of memories, particularly of fear memory. This advance was mainly due to pharmacological studies in many laboratories using localized brain injections of molecularly specific substances. One area in which significant advances have been made is in understanding that many different brain structures are involved in different memories, and that often several brain regions are involved in processing the same memory. These regions can cooperate or compete with each other, depending on circumstances that are beginning to be identified quite clearly. Another aspect in which major advances were made was retrieval and post-retrieval events, especially extinction, pointing to new therapeutic approaches to fearmotivated mental disorders.

scholarly journals Molecular Mechanisms of Heat Shock Factors in Cancer

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1202
Author(s):  
Mikael Christer Puustinen ◽  
Lea Sistonen
Keyword(s):  
Heat Shock ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Heat Shock Factors ◽  
Therapeutic Approaches ◽  
The Past ◽  
Cancer Types ◽  
Cellular Pathways ◽  
As Stress ◽  
Regulatory Functions

Malignant transformation is accompanied by alterations in the key cellular pathways that regulate development, metabolism, proliferation and motility as well as stress resilience. The members of the transcription factor family, called heat shock factors (HSFs), have been shown to play important roles in all of these biological processes, and in the past decade it has become evident that their activities are rewired during tumorigenesis. This review focuses on the expression patterns and functions of HSF1, HSF2, and HSF4 in specific cancer types, highlighting the mechanisms by which the regulatory functions of these transcription factors are modulated. Recently developed therapeutic approaches that target HSFs are also discussed.

scholarly journals Neuroinflammatory Nexus of Pediatric Epilepsy

2018 ◽  
Vol 07 (02) ◽  
pp. 032-039
Author(s):  
Shruti Bagla ◽  
Alan Dombkowski
Keyword(s):  
Inflammatory Mediators ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Recent Literature ◽  
Refractory Epilepsy ◽  
Genetic Mutation ◽  
Pediatric Epilepsy ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches

AbstractA rapidly growing body of evidence supports the premise that neuroinflammation plays an important role in initiating and sustaining seizures in a range of pediatric epilepsies. Clinical and experimental evidence indicates that neuroinflammation is both an outcome and a contributor to seizures. In this manner, seizures that arise from an initial insult (e.g., infection, trauma, and genetic mutation) contribute to an inflammatory response that subsequently promotes recurrent seizures. This cyclic relationship between seizures and neuroinflammation has been described as a “vicious cycle.” Studies of human tissue resected for surgical treatment of refractory epilepsy have reported activated inflammatory and immune signaling pathways, while animal models have been used to demonstrate that key inflammatory mediators lead to increased seizure susceptibility. Further characterization of the molecular mechanisms involved in this cycle may ultimately enable the development of new therapeutic approaches for the treatment of epilepsy. In this brief review, we focus on key inflammatory mediators that have become prominent in recent literature of epilepsy, including newly characterized microRNAs and their potential role in neuroinflammatory signaling.

scholarly journals Antiphospholipid Antibody Syndrome and Infertility

2019 ◽  
Vol 41 (10) ◽  
pp. 621-627
Author(s):  
Vivian de Oliveira Rodrigues ◽  
Adriana de Góes e Silva Soligo ◽  
Gabriel Duque Pannain
Keyword(s):  
Antiphospholipid Antibodies ◽  
Fetal Loss ◽  
Female Infertility ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Therapeutic Approaches ◽  
Negative Effects ◽  
The Past ◽  
New Therapeutic Approaches ◽  
Abortion Complications

AbstractAntiphospholipid antibody syndrome (APS) is a systemic, autoimmune, prothrombotic disease characterized by persistent antiphospholipid antibodies (aPLs), thrombosis, recurrent abortion, complications during pregnancy, and occasionally thrombocytopenia. The objective of the present study was to review the pathophysiology of APS and its association with female infertility. A bibliographic review of articles of the past 20 years was performed at the PubMed, Scielo, and Bireme databases. Antiphospholipid antibody syndrome may be associated with primary infertility, interfering with endometrial decidualization and with decreased ovarian reserve. Antiphospholipid antibodies also have direct negative effects on placentation, when they bind to the trophoblast, reducing their capacity for invasion, and proinflammatory effects, such as complement activation and neutrophil recruitment, contributing to placental insufficiency, restricted intrauterine growth, and fetal loss. In relation to thrombosis, APS results in a diffuse thrombotic diathesis, with global and diffuse dysregulation of the homeostatic balance. Knowing the pathophysiology of APS, which is closely linked to female infertility, is essential for new therapeutic approaches, specialized in immunomodulation and inflammatory signaling pathways, to provide important advances in its treatment.

Fifty Years of Experience with Chordomas in Southeast Scotland

Neurosurgery ◽  
1985 ◽  
Vol 16 (2) ◽  
pp. 166-170 ◽  
Author(s):  
P. O'Neill ◽  
B.A. Bell ◽  
J.D. Miller ◽  
I. Jacobson ◽  
W. Guthrie
Keyword(s):  
Clinical Presentation ◽  
Surgical Intervention ◽  
Slow Growth ◽  
Multicenter Trial ◽  
Treatment Modalities ◽  
Therapeutic Approaches ◽  
Slow Growth Rate ◽  
The Past ◽  
New Therapeutic Approaches

Abstract We report the clinical presentation and management of 34 patients with a histologically proven chordoma, treated in the neurosurgical departments in Edinburgh and Dundee, over the past 50 years. Although these tumors are commonly regarded as being locally invasive with a variable, but generally slow growth rate, they can metastasize, and this may precede surgical intervention, as in one of our patients. Our cases are compared to those in previously published series, and a comprehensive review of the treatment modalities for tumors at various sites is presented. The optimal treatment to be recommended from our own experience, and that of others, is aggressive operation and radiotherapy. A combination of hyperthermia and chemotherapy has shown some promise, but remains untested, and highlights the need for a multicenter trial with long follow-up to allow the evaluation of new therapeutic approaches.

scholarly journals Recent advances in the medical treatment of breast cancer

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2786 ◽  
Author(s):  
Daniel A. Vorobiof
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Medical Treatment ◽  
Breast Cancer Treatment ◽  
Chemotherapeutic Drugs ◽  
Therapeutic Approaches ◽  
The Past ◽  
New Therapeutic Approaches ◽  
Receptor Modulator ◽  
Medical Oncologists

Over the past few decades, the systemic therapy of breast cancer (early and advanced) has changed considerably. For the past 40–50 years, and since the discovery and further therapeutic use of tamoxifen, a selective estrogen receptor modulator, breast cancer treatment has become the model for the development and success of tailored medical treatment. Much still needs to be done in improving outcomes for all patients with breast cancer, and especially for those who have advanced breast cancer, a challenging area for medical oncologists. Ongoing international clinical trials are currently evaluating new therapeutic approaches and identifying specific biological subsets that could determine a patient’s ability to respond to particular chemotherapeutic drugs.

Towards new therapeutic approaches for malignant melanoma

2011 ◽  
Vol 13 ◽  
Author(s):  
Ivan Pacheco ◽  
Cristina Buzea ◽  
Victor Tron
Keyword(s):  
Molecular Mechanisms ◽  
Acquired Resistance ◽  
Therapeutic Approaches ◽  
Term Survival ◽  
Therapeutic Modalities ◽  
New Therapeutic Approaches ◽  
Mirna Genes ◽  
Molecular Therapeutics ◽  
Multistep Process

Recent progress in understanding the molecular mechanisms of the initiation and progression of melanoma has created new opportunities for developing novel therapeutic modalities to manage this potentially lethal disease. Although at first glance, melanoma carcinogenesis appears to be a chaotic system, it is indeed, arguably, a deterministic multistep process involving sequential alterations of proto-oncogenes, tumour suppressors and miRNA genes. The scope of this article is to discuss the most recent and significant advances in melanoma molecular therapeutics. It is apparent that using single agents targeting solely individual melanoma pathways might be insufficient for long-term survival. However, the outstanding results on melanoma survival observed with novel selective inhibitors of B-RAF, such as PLX4032 give hope that melanoma can be cured. The fact that melanoma develops acquired resistance to PLX4032 emphasises the importance of simultaneously targeting several pathways. Because the most striking feature of melanoma is its unsurpassed ability to metastasise, it is important to implement newer systems for drug delivery adapted from research on stem cells and nanotechnology.

scholarly journals An Overview of Long Non-Coding (lnc)RNAs in Neuroblastoma

2021 ◽  
Vol 22 (8) ◽  
pp. 4234
Author(s):  
Francesca Baldini ◽  
Matilde Calderoni ◽  
Laura Vergani ◽  
Paola Modesto ◽  
Tullio Florio ◽  
...  
Keyword(s):  
Recent Progress ◽  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
Biological Functions ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Definitive Therapy ◽  
Sporadic Cases ◽  
Non Coding Rnas

Neuroblastoma (NB) is a heterogeneous developmental tumor occurring in childhood, which arises from the embryonic sympathoadrenal cells of the neural crest. Although the recent progress that has been done on this tumor, the mechanisms involved in NB are still partially unknown. Despite some genetic aberrations having been identified, the sporadic cases represent the majority. Due to its wide heterogeneity in clinical behavior and etiology, NB represents a challenge in terms of prevention and treatment. Since a definitive therapy is lacking so far, there is an urgent necessity to unveil the molecular mechanisms behind NB onset and progression to develop new therapeutic approaches. Long non-coding RNAs (lncRNAs) are a group of RNAs longer than 200 nucleotides. Whether lncRNAs are destined to become a protein or not, they exert multiple biological functions such as regulating gene expression and functions. In recent decades, different research has highlighted the possible role of lncRNAs in the pathogenesis of many diseases, including cancer. Moreover, lncRNAs may represent potential markers or targets for diagnosis and treatment of diseases. This mini-review aimed to briefly summarize the most recent findings on the involvement of some lncRNAs in NB disease by focusing on their mechanisms of action and possible role in unveiling NB onset and progression.

scholarly journals Candida parapsilosis, an Emerging Fungal Pathogen

2008 ◽  
Vol 21 (4) ◽  
pp. 606-625 ◽  
Author(s):  
David Trofa ◽  
Attila Gácser ◽  
Joshua D. Nosanchuk
Keyword(s):  
Candida Parapsilosis ◽  
Molecular Genetic ◽  
Hydrolytic Enzymes ◽  
Severe Infection ◽  
Therapeutic Approaches ◽  
Indwelling Catheters ◽  
Prosthetic Devices ◽  
The Past ◽  
New Therapeutic Approaches ◽  
Care Workers

SUMMARY Candida parapsilosis is an emerging major human pathogen that has dramatically increased in significance and prevalence over the past 2 decades, such that C. parapsilosis is now one of the leading causes of invasive candidal disease. Individuals at the highest risk for severe infection include neonates and patients in intensive care units. C. parapsilosis infections are especially associated with hyperalimentation solutions, prosthetic devices, and indwelling catheters, as well as the nosocomial spread of disease through the hands of health care workers. Factors involved in disease pathogenesis include the secretion of hydrolytic enzymes, adhesion to prosthetics, and biofilm formation. New molecular genetic tools are providing additional and much-needed information regarding C. parapsilosis virulence. The emerging information will provide a deeper understanding of C. parapsilosis pathogenesis and facilitate the development of new therapeutic approaches for treating C. parapsilosis infections.

scholarly journals Transcriptional regulation of fetal to adult hemoglobin switching: new therapeutic opportunities

Blood ◽  
2011 ◽  
Vol 117 (15) ◽  
pp. 3945-3953 ◽  
Author(s):  
Andrew Wilber ◽  
Arthur W. Nienhuis ◽  
Derek A. Persons
Keyword(s):  
Clinical Manifestations ◽  
Fetal Hemoglobin ◽  
Therapeutic Approaches ◽  
The Past ◽  
Hemoglobin Switching ◽  
New Therapeutic Approaches ◽  
Developmental Gene Regulation ◽  
History Of ◽  
Adult Hemoglobin ◽  
The Subject

Abstract In humans, embryonic, fetal, and adult hemoglobins are sequentially expressed in developing erythroblasts during ontogeny. For the past 40 years, this process has been the subject of intensive study because of its value to enlighten the biology of developmental gene regulation and because fetal hemoglobin can significantly ameliorate the clinical manifestations of both sickle cell disease and β-thalassemia. Understanding the normal process of loss of fetal globin expression and activation of adult globin expression could potentially lead to new therapeutic approaches for these hemoglobin disorders. Herein, we briefly review the history of the study of hemoglobin switching and then focus on recent discoveries in the field that now make new therapeutic approaches seem feasible in the future. Erythroid-specific knockdown of fetal gene repressors or enforced expression of fetal gene activators may provide clinically applicable approaches for genetic treatment of hemoglobin disorders that would benefit from increased fetal hemoglobin levels.

scholarly journals Molecular Docking Technique to Understand Enzyme-Ligand Interactions

2017 ◽  
pp. 727-746
Author(s):  
Kailas Dashrath Sonawane ◽  
Maruti Jayram Dhanavade
Keyword(s):  
Molecular Docking ◽  
Molecular Mechanisms ◽  
Docking Studies ◽  
Atomic Level ◽  
Therapeutic Approaches ◽  
Lead Compounds ◽  
New Therapeutic Approaches ◽  
Docking Method ◽  
Ligand Interactions ◽  
Molecular Information

Molecular docking has advanced to such an extent that one can rapidly and accurately identify pharmaceutically useful lead compounds. It is being used routinely to understand molecular interactions between enzyme and ligand molecules. Several computational approaches are combined with experimental work to investigate molecular mechanisms in detail at the atomic level. Molecular docking method is also useful to investigate proper orientation and interactions between receptor and ligand. In this chapter we have discussed protein-protein approach to understand interactions between enzyme and amyloid beta (Aß) peptide. The Aß peptide is a causative agent of Alzheimer's disease. The Aß peptides can be cleaved specifically by several enzymes. Their interactions with Aß peptide and specific enzyme can be investigated using molecular docking. Thus, the molecular information obtained from docking studies might be useful to design new therapeutic approaches in treatment of Alzheimer's as well as several other diseases.

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