TY - JOUR AB - Attaining control over life and death decisions facilitates the identification of new therapeutic strategies for diseases affected by early cell loss or resistance to cell death. In this context, ferroptosis, a prevailing form of non-apoptotic cell death marked by the iron-dependent oxidative destruction of lipid bilayers and metabolic aberrations, has attracted overwhelming interest among basic researchers and clinicians due to its relevance for a number of degenerative diseases, such as neurodegeneration, ischemia/reperfusion injury (IRI), and organ failure, as well as therapy-resistant tumors. As the ferroptotic death pathway offers various druggable nodes, it is anticipated that the preclinical and clinical development of ferroptosis modulators will unleash unprecedented opportunities for the treatment of as-yet-incurable diseases. AU - Conrad, M. AU - Lorenz, S. AU - Proneth, B. C1 - 60148 C2 - 49276 CY - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England SP - 113-122 TI - Targeting ferroptosis: New hope for as-yet-incurable diseases. JO - Trends Mol. Med. VL - 27 IS - 2 PB - Elsevier Sci Ltd PY - 2021 SN - 1471-4914 ER - TY - JOUR AB - Immune check point inhibition (ICI) is a paradigm shift in oncology, but most patients treated with ICI will not respond to treatment. Thus, the need for predictive biomarkers for ICI is high. Dubuisson and colleagues have now reported on a new functional assay that might accurately inform on ICI response. AU - Kobold, S. C1 - 61165 C2 - 50079 CY - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England SP - 297-298 TI - An in sitro assay to predict primary resistance to PD-1 blockade. JO - Trends Mol. Med. VL - 27 IS - 4 PB - Elsevier Sci Ltd PY - 2021 SN - 1471-4914 ER - TY - JOUR AB - Brain injuries and neurodegenerative diseases elicit neuronal loss that persists because the adult mammalian brain lacks robust regenerative abilities. Direct reprogramming of local glial cells into neurons is a promising strategy for neuronal replacement in vivo. We discuss recent advances and future challenges in this approach to brain repair. AU - Bocchi, R. AU - Götz, M. C1 - 60064 C2 - 49717 CY - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England SP - 890-892 TI - Neuronal reprogramming for brain repair: Challenges and perspectives. JO - Trends Mol. Med. VL - 26 IS - 10 PB - Elsevier Sci Ltd PY - 2020 SN - 1471-4914 ER - TY - JOUR AB - Large genome-wide association studies (GWAS) have identified loci that are associated with complex traits and diseases, but index variants are often not causal and reside in non-coding regions of the genome. To gain a better understanding of the relevant biological mechanisms, in termediate traits such as gene expression and protein levels are increasingly being investigated because these are likely mediators between genetic variants and disease outcome. Genetic variants associated with intermediate traits, termed molecular quantitative trait loci (molQTLs), car then be used as instrumental variables in a Mendelian randomization (MR) approach to identify the causal features and mechanisms of complex traits. Challenges such as pleiotropy and the non-specificity of molQTLs remain, and further approaches and methods need to be developed. AU - Neumeyer AU - S. AU - Hemani, G.* AU - Zeggini, E. C1 - 57414 C2 - 47753 CY - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England SP - 232-241 TI - Strengthening causal inference for complex disease using molecular quantitative trait loci. JO - Trends Mol. Med. VL - 26 IS - 2 PB - Elsevier Sci Ltd PY - 2020 SN - 1471-4914 ER - TY - JOUR AB - Considerable progress has been made in understanding the contribution of E3 ubiquitin ligases to health and disease, including the pathogenesis of immunological disorders. Ubiquitin ligases exert exquisite spatial and temporal control over protein stability and function, and are thus crucial for the regulation of both innate and adaptive immunity. Given that immune responses can be both detrimental (autoimmunity) and beneficial (antitumor immunity), it is vital to understand how ubiquitin ligases maintain immunological homeostasis. Such knowledge could reveal novel mechanisms underlying immune regulation and identify new therapeutic approaches to enhance antitumor immunity and safeguard against autoimmunity. AU - Fujita, Y.* AU - Tinoco, R.* AU - Li, Y.* AU - Senft, D. AU - Ronai, Z.A.* C1 - 55706 C2 - 46524 CY - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England SP - 428-443 TI - Ubiquitin ligases in cancer immunotherapy - balancing antitumor and autoimmunity. JO - Trends Mol. Med. VL - 25 IS - 5 PB - Elsevier Sci Ltd PY - 2019 SN - 1471-4914 ER - TY - JOUR AB - Glucagon-like peptide-1 (GLP-1) analogs are considered the best current medicines for type 2 diabetes (T2D) and obesity due to their actions in lowering blood glucose and body weight. Despite similarities to GLP-1, glucose-dependent insulinotropic polypeptide (GIP) has not been extensively pursued as a medical treatment for T2D. This is largely based on observations of diminished responses of GIP to lower blood glucose in select patients, as well as evidence from rodent knockout models implying that GIP promotes obesity. These findings have prompted the belief in some, that inhibiting GIP action might be beneficial for metabolic diseases. However, a growing body of new evidence - including data based on refined genetically modified models and improved pharmacological agents - suggests a paradigm shift on how the GIP system should be manipulated for metabolic benefits. AU - Finan, B. AU - Müller, T.D. AU - Clemmensen, C. AU - Perez-Tilve, D.* AU - Tschöp, M.H. C1 - 48243 C2 - 41014 CY - Oxford SP - 359-376 TI - Reappraisal of GIP pharmacology for metabolic diseases. JO - Trends Mol. Med. VL - 22 IS - 5 PB - Elsevier Sci Ltd PY - 2016 SN - 1471-4914 ER - TY - JOUR AB - In addition to safeguarding the central nervous system (CNS) from the vast majority of pathogens and toxins, transvascular barriers impose immense challenges to the delivery of beneficial cargo. A few toxins and neurotropic viruses capable of penetrating the brain have proved to be potentially valuable for neuron targeting and enhanced transfer of restorative medicine and therapeutic genes. Here we review molecular concepts and implications of the highly neurotropic tetanus toxin (TeTx) and botulinum neurotoxins (BoNTs) and their ability to infiltrate and migrate throughout neurons. We discuss recent applications of their detoxified variants as versatile nanovehicles for retroaxonal delivery of therapeutics to motor neurons and synapses. Continued advances in research on these remarkable agents in preclinical trials might facilitate their future use for medical benefit. AU - Ovsepian, S.V. AU - O'Leary, V.B. AU - Ntziachristos, V. AU - Dolly, J.O.* C1 - 49703 C2 - 40802 CY - Oxford SP - 983-993 TI - Circumventing brain barriers: Nanovehicles for retroaxonal therapeutic delivery. JO - Trends Mol. Med. VL - 22 IS - 11 PB - Elsevier Sci Ltd PY - 2016 SN - 1471-4914 ER - TY - JOUR AB - Mutations that cause rhodopsin misfolding and retention within the endoplasmic reticulum (ER) are a prominent cause of retinitis pigmentosa. Here, we discuss the hypothesis that the failure of photoreceptor neurons to adapt to the stress caused by rhodopsin accumulation in the ER leads to a global collapse of homeostasis and to retinal degeneration. We review the molecular mechanisms underlying the activity of local ER conformational sensors and stress-relaying modules and consider how ER-derived stress signals are amplified and implemented to impact on downstream processes, including rhodopsin clearance and cell fate control. The emerging view is that alterations to the systems responsible for the detection, transduction and implementation of ER stress might be used therapeutically to treat retinitis pigmentosa. AU - Griciuc, A. AU - Aron, L.* AU - Ueffing, M. C1 - 4698 C2 - 28991 CY - Oxford, UK SP - 442-451 TI - ER stress in retinal degeneration: A target for rational therapy? JO - Trends Mol. Med. VL - 17 IS - 8 PB - Elsevier PY - 2011 SN - 1471-4914 ER - TY - JOUR AU - Jagasia, R. AU - Song, H.* AU - Gage, F.H.* AU - Lie, D.C. C1 - 5245 C2 - 23872 SP - 400-405 TI - New regulators in adult neurogenesis and their potential role for repair. JO - Trends Mol. Med. VL - 12 PY - 2006 SN - 1471-4914 ER - TY - JOUR AU - Hammerschmidt, W. AU - Sugden, B.* C1 - 5212 C2 - 22372 SP - 331-336 TI - Epstein-Barr virus sustains Burkitt's lymphomas and Hodgkin's disease. JO - Trends Mol. Med. VL - 10 PY - 2004 SN - 1471-4914 ER - TY - JOUR AU - Müller, M.B.* AU - Wurst, W. C1 - 5205 C2 - 22415 SP - 409-415 TI - Getting closer to affective disorders: The role of CRH receptor systems. JO - Trends Mol. Med. VL - 10 PY - 2004 SN - 1471-4914 ER -