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Impacts of hnRNP A1 Splicing Inhibition on the Brain Remyelination Proteome.
J Neurochem
January 2025
Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
Oligodendrocytes, the myelinating cells in the central nervous system, are implicated in several neurological disorders marked by dysfunctional RNA-binding proteins (RBPs). The present study aimed at investigating the role of hnRNP A1 in the proteome of the corpus callosum, prefrontal cortex, and hippocampus of a murine cuprizone-induced demyelination model. Right after the cuprizone insult, we administered an hnRNP A1 splicing activity inhibitor and analyzed its impact on brain remyelination by nanoESI-LC-MS/MS label-free proteomic analysis to assess the biological processes affected in these brain regions.
View Article and Find Full Text PDFHigh-prediction QSAR Modeling Study Based on the Efficacy of a Novel 6-hydroxybenzothiazole-2-carboxamide Targeted Monoamine Oxidase B in the Treatment of Neurodegenerative Diseases.
Med Chem
January 2025
Department of Neurosurgery, The 940th Hospital of Joint Logistics Support force of Chinese People's Liberation Army, Lanzhou, China.
Background: Neurodegenerative diseases are a group of disorders characterized by progressive neuronal degeneration and death, of which Alzheimer's disease and Parkinson's disease are the most common. These diseases are closely associated with increased expression of monoamine oxidase B (MAO-B), an important enzyme that regulates neurotransmitter concentration, and its overactivity leads to oxidative stress and neurotoxicity, accelerating the progression of neurodegenerative diseases. Therefore, the development of effective MAO-B inhibitors is important for the treatment of neurodegenerative diseases.
View Article and Find Full Text PDFDual inhibition of AChE and MAO-B in Alzheimer's disease: machine learning approaches and model interpretations.
Mol Divers
January 2025
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116024, Liaoning, China.
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases. Given the multifactorial pathophysiology of AD, monotargeted agents can only alleviate symptoms but not cure AD. Acetylcholinesterase (AChE) and Monoamine oxidase B (MAO-B) are two key targets in the treatment of AD, molecules that inhibiting both targets are considered promising avenue to develop more effective AD therapies.
View Article and Find Full Text PDFIncomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function.
Nat Commun
January 2025
Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO, USA.
Myelin loss induces neural dysfunction and contributes to the pathophysiology of neurodegenerative diseases, injury conditions, and aging. Because remyelination is often incomplete, better understanding endogenous remyelination and developing remyelination therapies that restore neural function are clinical imperatives. Here, we use in vivo two-photon microscopy and electrophysiology to study the dynamics of endogenous and therapeutic-induced cortical remyelination and functional recovery after cuprizone-mediated demyelination in mice.
View Article and Find Full Text PDFOptimizing Linezolid: Transforming It into a Selective MAO-B Inhibitor via a Toxicity-to-Activity Optimization Approach.
ACS Med Chem Lett
January 2025
Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra 425405, India.
Linezolid, a widely used oxazolidinone antibiotic, exhibits potent activity against resistant bacterial infections but is associated with serotonergic toxicity, primarily due to its inhibition of monoamine oxidase (MAO). MAOs, consisting of MAO-A and MAO-B isoforms, play crucial roles in neurotransmitter metabolism, with implications for neurodegenerative disorders like Parkinson's and Alzheimer's diseases. This study aims to optimize Linezolid's structure to transform it into a selective MAO-B inhibitor.
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