Publications by authors named "M D'Ascenzo"
Reactive oxygen and nitrogen species (ROS; RNS) are natural bioproducts of cellular metabolism, particularly produced within the mitochondria during energy production [...
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- Protein/protein interactions (PPI) are important for brain functions, but their use as drug targets for brain disorders is not fully explored.
- A small molecule called compound 1028 has been identified that targets the FGF14/Na1.6 PPI and affects the channel's activity, resulting in increased excitability of neurons.
- Administering compound 1028 can enhance motivation under challenging conditions, and its effects are linked to changes in dopamine levels in the brain, suggesting a new way to impact behaviors related to neuropsychiatric disorders.
Article Synopsis
- Dopamine D3 receptors (D3Rs) play a key role in modulating brain activity, particularly in the hippocampus, which is crucial for memory and learning.
- Blocking or removing D3Rs in mice enhances synaptic activity and improves long-term memory formation by strengthening synaptic connections through the cAMP/PKA signaling pathway.
- In aged mice, D3Rs show a decline in axon terminals but remain stable in dendrites, and blocking these receptors can reverse memory and synaptic deficits, highlighting their potential as a target for treating cognitive decline in older individuals.
Background: Reduction of adult hippocampal neurogenesis is an early critical event in Alzheimer's disease (AD), contributing to progressive memory loss and cognitive decline. Reduced levels of the nucleoporin 153 (Nup153), a key epigenetic regulator of NSC stemness, characterize the neural stem cells isolated from a mouse model of AD (3×Tg) (AD-NSCs) and determine their altered plasticity and gene expression.
Methods: Nup153-regulated mechanisms contributing to NSC function were investigated: (1) in cultured NSCs isolated from AD and wild type (WT) mice by proteomics; (2) in vivo by lentiviral-mediated delivery of Nup153 or GFP in the hippocampus of AD and control mice analyzing neurogenesis and cognitive function; (3) in human iPSC-derived brain organoids obtained from AD patients and control subjects as a model of neurodevelopment.
It has been recently established that GPR158, a class C orphan G protein-coupled receptor, serves as a metabotropic glycine receptor. GPR158 is highly expressed in the nucleus accumbens (NAc), a major input structure of the basal ganglia that integrates information from cortical and subcortical structures to mediate goal-directed behaviors. However, whether glycine modulates neuronal activity in the NAc through GPR158 activation has not been investigated yet.
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