Differential recognition of diverse G-quadruplex structures can be achieved by controlling the folding of a small molecule.
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http://dx.doi.org/10.1039/b816861j | DOI Listing |
Nat Rev Drug Discov
January 2025
Mission Therapeutics Ltd, Babraham Research Campus, Cambridge, UK.
Mitochondrial dysfunction is a hallmark of idiopathic neurodegenerative diseases, including Parkinson disease, amyotrophic lateral sclerosis, Alzheimer disease and Huntington disease. Familial forms of Parkinson disease and amyotrophic lateral sclerosis are often characterized by mutations in genes associated with mitophagy deficits. Therefore, enhancing the mitophagy pathway may represent a novel therapeutic approach to targeting an underlying pathogenic cause of neurodegenerative diseases, with the potential to deliver neuroprotection and disease modification, which is an important unmet need.
View Article and Find Full Text PDFNPJ Vaccines
January 2025
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Cyclic peptides are often used as scaffolds for the multivalent presentation of drug molecules due to their structural stability and constrained conformation. We identified a cyclic deca-peptide incorporating lipoamino acids for delivering T helper and B cell epitopes against group A Streptococcus (GAS), eliciting robust humoral immune responses. In this study, we assessed the function-immunogenicity relationship of the multi-component vaccine candidate (referred to as VC-13) to elucidate a mechanism of action.
View Article and Find Full Text PDFCell Death Dis
January 2025
Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield Clinic Health System, Marshfield, WI, USA.
The orphan nuclear receptor NR2E3 has emerged as a potential tumor suppressor, yet its precise mechanisms in tumorigenesis require further investigation. Here, we demonstrate that the full-length protein isoform of NR2E3 instead of its short isoform activates wild-type p53 and is capable of rescuing certain p53 mutations in various cancer cell lines. Importantly, we observe a higher frequency of NR2E3 mutations in three solid tumors compared to the reference population, highlighting its potential significance in tumorigenesis.
View Article and Find Full Text PDFAdv Biol Regul
December 2024
Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
TP53 is normally a tumor suppressor. However, it is mutated in at least 50% of human cancers. Usually, we assume that mutation of the TP53 is associated with loss of sensitivity to various drugs as in most cases wild type (WT) TP53 activity is lost.
View Article and Find Full Text PDFJ Neurosci
January 2025
Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University School of Medicine, Morgantown, WV, USA.
Synaptically released zinc is a neuronal signaling system that arises from the actions of the presynaptic vesicular zinc transporter protein ZnT3. Mechanisms that regulate the actions of zinc at synapses are of great importance for many aspects of synaptic signaling in the brain. Here, we identify the astrocytic zinc transporter protein ZIP12 as a candidate mechanism that contributes to zinc clearance at cortical synapses.
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