Estimating the therapeutic potential of NSAIDs and linoleic acid-isomers supplementation against neuroinflammation.

Nonsteroidal anti-inflammatory drugs (NSAIDs) regulate inflammation, which is associated with their role in preventing neurodegenerative diseases in epidemiological studies. It has sparked interest in their unconventional application for reducing neuroinflammation, opening up new avenues in biomedical research. However, given the pharmacological drawbacks of NSAIDs, the development of formulations with naturally antioxidant/anti-inflammatory dietary fatty acids has been demonstrated to be advantageous for the clinical translation of anti-inflammatory-based therapies. It includes improved blood-brain barrier (BBB) permeability and reduced toxicity. It permits us to speculate about the value of linoleic acid (LA)-isomers in preventing and treating neuroinflammatory diseases compared to NSAIDs. Our research delved into the impact of various factors, such as administration route, dosage, timing of intervention, and BBB permeability, on the efficacy of NSAIDs and LA-isomers in preclinical and clinical settings. We conducted a systematic comparison between NSAIDs and LA-isomers regarding their therapeutic effectiveness, BBB compatibility, and side effects. Additionally, we explored their underlying mechanisms in addressing neuroinflammation. Through our analysis, we've identified challenges and drawn conclusions that could propel advancements in treating neurodegenerative diseases and inform the development of future alternative therapeutic strategies.

The multiple functions of PrPC in physiological, cancer, and neurodegenerative contexts.

Cellular prion protein (PrPC) is a highly conserved glycoprotein, present both anchored in the cell membrane and soluble in the extracellular medium. It has a diversity of ligands and is variably expressed in numerous tissues and cell subtypes, most notably in the central nervous system (CNS). Its importance has been brought to light over the years both under physiological conditions, such as embryogenesis and immune system homeostasis, and in pathologies, such as cancer and neurodegenerative diseases. During development, PrPC plays an important role in CNS, participating in axonal growth and guidance and differentiation of glial cells, but also in other organs such as the heart, lung, and digestive system. In diseases, PrPC has been related to several types of tumors, modulating cancer stem cells, enhancing malignant properties, and inducing drug resistance. Also, in non-neoplastic diseases, such as Alzheimer's and Parkinson's diseases, PrPC seems to alter the dynamics of neurotoxic aggregate formation and, consequently, the progression of the disease. In this review, we explore in detail the multiple functions of this protein, which proved to be relevant for understanding the dynamics of organism homeostasis, as well as a promising target in the treatment of both neoplastic and degenerative diseases.

Glioblastoma Therapy in the Age of Molecular Medicine.

Glioblastoma (GBM) is the most common and fatal primary malignant brain tumor. Despite advances in the understanding of the biology of gliomas, little has changed in the treatment of these tumors in the past decade. Phase III clinical trials showed no benefit for the use of bevacizumab in newly diagnosed patients, leading to a renewed search for new antiangiogenic drugs, as well as immunotherapeutic approaches, including checkpoint inhibitors, chimeric antigen receptor T cells, and intracerebral CpG-oligodeoxynucleotides. The emerging role of infiltrating microglia and macrophages, and of metabolic alterations, is also being taken into account in preclinical research and drug development. In this review, we discuss progress in the search for new therapeutic strategies, particularly approaches focusing on the tumor microenvironment.