Publications by authors named "Borsello T"
Article Synopsis
- * The study, funded by the Italian Ministry of Health, aims to explore how inflammation contributes to depression onset, treatment resistance, and related health issues through various scientific analyses and human cohorts.
- * Over two years, the research will enhance understanding of inflammation's role in MDD and related disorders, potentially leading to new personalized treatment strategies.
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.
Introduction: Autism spectrum disorders (ASD) are the most prevalent neurobiological disorders in children. The etiology comprises genetic, epigenetic, and environmental factors such as dysfunction of the immune system. Epigenetic mechanisms are mainly represented by DNA methylation, histone modifications, and microRNAs (miRNA).
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- - The study aims to evaluate the presence of synaptic damage biomarkers in individuals with Alzheimer's disease (AD) compared to cognitively unimpaired (CU) people through a systematic review and meta-analysis.
- - After reviewing 204 articles, 23 studies were included in the systematic review and 15 in the meta-analysis, revealing significant increases in the cerebrospinal fluid levels of Neurogranin, SNAP-25, and GAP-43 in AD patients compared to CU individuals.
- - The findings suggest that these synaptic biomarkers could help in diagnosing AD, but the current research is relatively limited and shows a lot of variation in results across studies.
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.
Article Synopsis
- * The study found that knocking out the MAPK isoform JNK1 significantly reduces myelin in the cerebral cortex and corpus callosum during postnatal and adult stages, leading to higher OPC density and proliferation early in life.
- * JNK1 knockout OPCs have smaller territories and simpler structures, and although differentiation seems normal, both knockout and treated OLs have reduced surface area, highlighting JNK1's crucial role in OPC function and myelination.
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
- Local protein synthesis at synapses has been shown to play a crucial role in brain plasticity, challenging the idea that protein synthesis mainly occurs in the cell body and dendrites.
- The study examined protein synthesis in TgCRND8 mice, which model Alzheimer's disease, finding differences in newly synthesized proteins at synapses compared to control mice, with some evidence of local APP synthesis.
- Results indicated that while control mice showed enhanced protein synthesis at synapses after learning tasks, TgCRND8 mice did not, suggesting that impaired local protein synthesis may contribute to the early development of Alzheimer's pathology.
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.
Article Synopsis
- Spinal muscular atrophy (SMA) is a serious childhood neurodegenerative disorder caused by the loss of the SMN1 gene, leading to muscle atrophy and paralysis due to motor neuron degeneration.
- Recent research highlights the involvement of the c-Jun NH-terminal kinase (JNK) signaling pathway in the progression of SMA, prompting the study of a specific JNK inhibitor (D-JNKI1) in a mouse model of the disease.
- Administration of D-JNKI1 was found to delay motor neuron death, reduce spinal cord inflammation, enhance muscle fiber health, and slightly increase the lifespan of SMA mice, suggesting that targeting the JNK pathway could be a potential treatment strategy for SMA.
Article Synopsis
- * Recent research shows that DJ-1 interacts with components of stress granules and can localize to these granules, as well as P-bodies, in response to various stress conditions in mammalian cells.
- * The findings suggest that DJ-1 may play a significant role in RNA dynamics by associating with specific mRNAs during stressful situations, which could help explain its connection to neurodegeneration and Parkinson's disease.
Article Synopsis
- - Numerous studies have shown that the cerebellum experiences both structural and functional changes in Alzheimer's disease, and this study focuses on early alterations in TgCRND8 mice before significant plaque formation.
- - Behavioral tests demonstrated notable motor coordination and balance issues in 2-month-old TgCRND8 mice, along with patch-clamp recordings indicating dysfunction in cerebellar synapses caused by amyloid precursor protein overexpression.
- - The study identified increased expression of specific proteins linked to oxidative stress in the cerebellum, suggesting a feedback loop that enhances reactive oxygen species production, potentially worsening Alzheimer's disease pathology in its early stages.
Background: Disruption of axonal transport plays a pivotal role in diabetic neuropathy. A sex-dimorphism exists in the incidence and symptomatology of diabetic neuropathy; however, no studies so far have addressed sex differences in axonal motor proteins expression in early diabetes as well as the possible involvement of neuroactive steroids. Interestingly, recent data point to a role for mitochondria in the sexual dimorphism of neurodegenerative diseases.
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- Recent research suggests that eye-related issues like amyloid-beta accumulation in the retina and nerve fiber layer loss might serve as biomarkers for Alzheimer's Disease (AD).
- Using the TgCRND8 mouse model, scientists found a relationship between eye pathologies and AD, highlighting the vulnerability of retinal ganglion cells to degeneration through various imaging and analysis methods.
- Notably, they discovered that inhibiting the C-Jun N-terminal Kinase (JNK) helped reduce amyloid and Tau buildup, thereby protecting retinal ganglion cells, indicating that eye changes can reflect brain changes in AD.
Article Synopsis
- Tauopathies are neurodegenerative diseases characterized by the harmful buildup of tau protein in the brain, and research has primarily focused on the relationship between diet and beta-amyloid in Alzheimer's disease, leaving the effect of diet on tau largely unexplored.
- A study on a low fat-protein diet (LFPD) in P301L-tg mouse models showed that this diet improved lifespan, cognitive functions, and physical activity compared to those on a standard diet, which linked weight loss and increased mortality in these mice.
- The LFPD also reduced harmful tau protein aggregates and apoptosis markers in the brain, with notable findings indicating that female mice benefited more than males, pointing towards potential lifestyle influences in delaying cognitive decline, particularly
Article Synopsis
- The study investigates the presence and role of c-Jun N-terminal kinase (JNK) at presynaptic sites in neurons, particularly in relation to NMDA receptor activation and synaptic plasticity.
- Researchers used advanced microscopy and biochemical techniques to show that JNK is localized at presynaptic locations and is active there, interacting with T-SNARE proteins that are crucial for neurotransmitter release.
- Findings highlight that JNK's phosphorylation of T-SNARE proteins is essential for modulating vesicle release, impacting synaptic plasticity, which is fundamental for learning and memory processes.
Article Synopsis
- P301L transgenic mice serve as an effective model for studying human tauopathies, showcasing features like lower body weight, decreased survival, and neurodegeneration at 15 months of age.
- The study revealed that female P301L mice experienced more severe neuropathological changes than males, with higher levels of hyperphosphorylated tau (p-tau) and greater spinal injuries.
- High levels of p-tau were linked to a reduction in essential post-synaptic markers, indicating that targeting p-tau could be a potential therapeutic approach to mitigate synaptic damage and understand the influence of sex on tau-related disorders.