Publications by authors named "G M Aceto"
Article Synopsis
- 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.
Background: Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by the accumulation of pathological proteins and synaptic dysfunction. This study aims to investigate the molecular and functional differences between human induced pluripotent stem cells (hiPSCs) derived from patients with sporadic AD (sAD) and age-matched controls (healthy subjects, HS), focusing on their neuronal differentiation and synaptic properties in order to better understand the cellular and molecular mechanisms underlying AD pathology.
Methods: Skin fibroblasts from sAD patients (n = 5) and HS subjects (n = 5) were reprogrammed into hiPSCs using non-integrating Sendai virus vectors.
Protein post-translational modifications (PTM) play a crucial role in the modulation of synaptic function and their alterations are involved in the onset and progression of neurodegenerative disorders. S-palmitoylation is a PTM catalyzed by zinc finger DHHC domain containing (zDHHC) S-acyltransferases that affects both localization and activity of proteins regulating synaptic plasticity and amyloid-β (Aβ) metabolism. Here, we found significant increases of both zDHHC7 expression and protein S-palmitoylation in hippocampi of both 3×Tg-AD mice and post-mortem Alzheimer's disease (AD) patients.
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- 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.