Publications by authors named "Clara A Musi"
Article Synopsis
- The c-Jun N-terminal kinases (JNKs) are proteins activated by stress that can negatively affect neuron function and survival, particularly in the context of Alzheimer's disease (AD).
- A study on 5xFAD mice, which model human AD, revealed significant JNK activation at 3.5 months that correlated with changes in neuron structure and memory loss.
- These results suggest that targeting JNK might be a promising strategy for developing treatments aimed at preventing synaptic impairment in the early stages of AD.
The human brain is the most complex organ in biology. This complexity is due to the number and the intricate connections of brain cells and has so far limited the development of in vitro models for basic and applied brain research. We decided to create a new, reliable, and cost-effective in vitro system based on the Nichoid, a 3D microscaffold microfabricated by two-photon laser polymerization technology.
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- - JNKs, particularly JNK3, are stress-response protein kinases mainly found in the brain and other specific tissues, playing a crucial role in stress signaling and synaptic function related to neurodegeneration.
- - The JNK3 signaling pathway involves a series of carefully regulated phosphorylation steps, with specificity ensured by scaffold proteins like JIP1 and β-arrestin2.
- - Using techniques like super-resolution microscopy and co-immunoprecipitation, researchers demonstrated that JNK3 interacts with PSD95 and the scaffold proteins JIP1 and β-arrestin2 in neurons, suggesting these interactions could be targets to modulate synaptic events affected by stress.
Article Synopsis
- - Rett syndrome (RTT) is a genetic disorder caused by mutations in the MECP2 gene, leading to cognitive and neural impairments; finding alternative therapies is crucial as gene therapy has potential side effects.
- - Research showed that the c-Jun N-terminal kinase (JNK) pathway is activated in RTT models, and using the JNK inhibitor D-JNKI1 significantly improved symptoms like body weight recovery and locomotion abilities in mice.
- - Treatment with D-JNKI1 also reduced severe breathing issues and prevented neuronal death in lab-created neurons from patients with MECP2 mutations, highlighting its potential as a therapeutic approach for RTT.
Article Synopsis
- - Type 2 diabetes (T2D) is linked to various health issues, including diabetic retinopathy (DR) and a higher risk of cognitive decline, particularly Alzheimer's disease (AD).
- - Both DR and AD involve similar harmful processes, such as inflammation and blood vessel damage, which are aggravated by diabetes-related issues like high blood sugar and insulin resistance.
- - Identifying the common mechanisms affecting the brain and retina in T2D can help in determining which patients are more likely to experience cognitive decline.
Article Synopsis
- The SUMOylation machinery regulates neuronal activity and synaptic plasticity, involving SUMO isoforms and specific enzymes known as E1, E2, and E3 SUMO ligases.
- Recent research has focused more on SUMO isoforms and E2 enzymes, while E3 ligases, particularly PIAS proteins, have been less explored despite their role in spatial memory formation in rodents.
- This study used structured illumination microscopy for the first time to examine the co-localization of PIAS1 and PIAS3 with synaptic markers, revealing partial co-localization in hippocampal neurons but less frequent in cortical neurons, aligning with earlier findings on SUMOylation components.
SUMOylation of proteins plays a key role in modulating neuronal function. For this reason, the balance between protein SUMOylation and deSUMOylation requires fine regulation to guarantee the homeostasis of neural tissue. While extensive research has been carried out on the localization and function of small ubiquitin-related modifier (SUMO) variants in neurons, less attention has been paid to the SUMO-specific isopeptidases that constitute the human SUMO-specific isopeptidase (SENP)/Ubiquitin-Specific Protease (ULP) cysteine protease family (SENP1-3 and SENP5-7).
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- JNK3 is a brain-specific isoform of c-Jun N-terminal kinase that responds to stress stimuli in the central nervous system and is regulated by scaffold proteins like JIP-1 and β-arrestin-2.
- This kinase is involved in synaptic dysfunction, a precursor to various neurodegenerative diseases, highlighting its role in maintaining synapse structure and function.
- JNK3's presence in peripheral regions suggests its potential as a biomarker for early diagnosis of neurodegenerative conditions, with the possibility of reversing synaptic dysfunction offering new therapeutic avenues.
Article Synopsis
- Deficiency of the UBE3A enzyme is linked to Angelman syndrome, while excessive levels are associated with autism spectrum disorder, but the mechanisms behind these effects are poorly understood.
- A study using a mouse model with maternal UBE3A loss reveals activation of JNK signaling in brain regions that correlates with behavioral and biochemical changes, indicating significant spinal pathology.
- Inhibiting JNK signaling in these mice leads to the restoration of cognitive function and synaptic protein levels, highlighting its critical role in UBE3A-related disorders and opening avenues for potential treatments.
Article Synopsis
- Pathological Tau (P-Tau) is linked to dementia and neurodegeneration, with P301L transgenic mice serving as a model that reflects human tauopathy, showing sex differences in severity, particularly worse in females.
- JNK activation in these mice suggests its involvement in degenerative processes, with increased levels of key proteins indicating heightened synaptic dysfunction and behavioral defects, especially in female mice.
- As current treatments for synaptic pathology are lacking, targeting the JNK pathway with specific inhibitors could be a promising strategy for addressing P-Tau-related neurological issues.