Rett syndrome

…Rett syndrome provides a starting point: MeCP2 mutations impair endothelial function, suggesting that vascular cells themselves contribute to disease mechanisms. A three-dimensional microphysiological model built from human induced pluripotent stem cells recreates blood–brain barrier structure and function. Patient-derived endothelial cells form perfusable microvascular networks but show impaired barrier function, a find

…The talk will focus on Rett Syndrome and discuss two topics: (i) the use of gene editing as an approach to therapy and (ii) the role of MECP2 in gene expression (i) The mutation of the X-linked MECP2 gene is causative for the disease. In a female patient, every cell has a wt copy that is, however, in 50% of the cells located on the inactive X chromosome. We have used epigenetic gene editing tools to activate the wt MECP2 allele on the inactive X

Aims: Autophagy is an evolutionary conserved process, that is very important in neurons. Neurons are post-mitotic cells which require a strict quality control mechanism to prevent accumulation of cellular debris and ensure nutrient and energy balance. Also synapses are key elements for healthy brain functioning. The synapses of neurons are highly dynamic, especially during early period of lifetimeand. Their rate increased during embryogenesis but subsequently unnecessary synapses are eliminated through a process called pruning modulated by autophagy. Many studies have shown that autophagy is a

…for its potential in the treatment of Rett syndrome, a neurodevelopmental disorder affecting 1/10.000 young females worldwide. However, the mechanisms of action of MTZ are still unclear. To gain new insights into the pharmacological effects of MTZ, the in-silico prediction of novel targets for MTZ represents a valuable approach. S-MTZ and R-MTZ chemical structures were downloaded from PubChem database to perform a screening of S-/R- MTZ versus 25.717 h

Rett syndrome (RTT) is a devastating neurodevelopmental disorder primarily affecting females, characterised by the loss of motor skills and behavioural abnormalities linked to an excitatory/inhibitory imbalance involving GABA dysfunction. GABAergic deficits, particularly in somatostatin (SST) interneurons, play a crucial role in RTT pathophysiology and have been successfully replicated in mouse models. This study delves deeper into understanding the role of GABAergic interneuron inhibition in an RTT mouse model. Neonatal injections were administered to Mecp2tm1.1Bird x Sst-IRES-Cre mice at P1,

Rett Syndrome (RTT) is a severe neurodevelopmental disorder primarily affecting females. The disease is mainly caused by pathogenic variants in the X-linked MECP2 gene, which encodes for the global transcriptional regulator MeCP2, important for neuronal maturation and maintenance. So far, no cure is currently available. Recently, cell penetrating peptides (CPPs) attracted a special interest in the use of protein replacement therapy by facilitating the transport of proteins across cell membranes and the blood-brain barrier (BBB).In this study, we generated a neuronal cell model by direct reprog

Rett syndrome (RTT) is an early-onset neurological disorder that primarily affects females, causing severe cognitive and physical disabilities. Recently, an imbalance in redox homeostasis and exacerbated inflammatory response have been shown to play a central role in the diverse clinical manifestations of the disease.Numerous studies have highlighted that p75 neurotrophin receptor (p75NTR) may have a role in the regulation of oxidative stress (OS) and inflammation.Therefore, the aim of this work was to evaluate whether the modulation of p75NTR by LM11A-31 counteracts the alterations in OS and

Rett syndrome (RTT) is a severe neurodevelopmental disorder linked to abnormal levels of methyl CpG binding protein 2 (MeCP2), a global transcriptional regulator, known to both enhance and silence gene expression. It has been demonstrated on numerous occasions, however, that replenishing functional MeCP2 levels in the central nervous system, can ameliorate and even reverse the RTT phenotype. One such RTT treatment approach involves administering recombinantly purified MeCP2 while tethered to the cell-penetrating peptide TAT which is known to transduce fused protein cargo across cell membrane a

Introduction: Rett syndrome (RTT) is a rare neurodevelopmental disorder caused in 95% of cases by mutations in the X-linked methyl CpG-binding protein 2 (MeCP2) gene. Although apparently normal at birth, RTT patients manifest a regression phase between 6-18 months of age characterized by loss of speech, impaired motor functions, seizures and intellectual disabilities. Clinical and animal studies suggested that metabolic pathways might be affected and contribute to RTT pathophysiology. Autophagy is a catabolic process involved in the degradation of cellar debris and recently found to regulate a

Rett Syndrome (RTT) is a genetic neurodevelopmental disorder characterized by progressive regression of mental and psychomotor development during the symptomatic phase, following a period of apparent normal growth in the first months of life (presymptomatic phase). Evidence suggests that metabolic abnormalities, including mitochondrial dysfunction, aberrant redox homeostasis, and subclinical inflammation, significantly contribute to RTT. The unique pathogenic development of RTT involves a relatively slow transition to the symptomatic stage, providing a critical time window for early diagnosis

Rett Syndrome (RTT) is a X-linked neurodevelopmental disorder that predominantly affects girls. The detailed disease mechanisms remain unclear and fundamental treatments are yet to be established. The majority of typical RTT cases is triggered by mutations in the methyl CpG-binding protein 2 (MeCP2) gene. For the analyze of the disease mechanisms and drug development, in vitro models based on iPSC-derived cells with diseased MeCP2 are being investigated. In addition to MeCP2 mutations RTT is also affected by the genetic background, and thus it is necessary to analyze the effect of MeCP2 modifi

…from MECP2 gene alterations, such as Rett syndrome (RTT) and MECP2-duplication syndrome (MDS), present challenges in understanding the complex links between genetic alterations and cognitive deficits. Previous animal-based studies, though insightful, face translational barriers due to evolutionary differences in brain development between species, hindering direct application to humans.To address this, we established an innovative in vivo human neuronal model for RTT and MDS, utilizing patient-derived induced pluripotent stem cells

With this webinar series, the ALBA Disability & Accessibility Working Group aims to bring down the ivory tower of ableism among the brain research community, one extraordinary neuroscientist at a time. These webinars give a platform to scientists with disabilities across the globe and neuroscience disciplines, while reflecting on how to promote inclusive working environments and accessibility to research. For this 4th episode, Dr. Maria José Diógenes (iMM - ULisboa, PT) will talk about how her personal story changed her professional life: from the pharmacy to the laboratory bench and from agei

Learning requires the formation or modification of neural circuits – an extraordinary showcase of the brain’s plasticity. Despite an established appreciation for the reorganizational capabilities of the brain, the exact mechanisms that enable experience-dependent plasticity remain unknown. The goal of this work is to uncover how circuitry of the auditory cortex (AC) facilitates learning of an auditory-driven maternal retrieval behavior in mice. Mouse pups emit ultrasonic vocalizations (USVs) when they are separated from the nest which cues maternal retrieval - a learned response to these distr

In our everyday lives, we form connections and build up social networks that allow us to function successfully as individuals and as a society. Our social networks tend to include well-connected individuals who link us to other groups of people that we might otherwise have limited access to. In addition, we are more likely to befriend individuals who a) live nearby and b) have mutual friends. Interestingly, neurons tend to do the same…until development is perturbed. Just like social networks, neuronal networks require highly connected hubs to elicit efficient communication at minimal cost (you

Reprogramming somatic cells to a pluripotent state via the induced pluripotent stem cell (iPSC) method offers an increasingly utilized approach for neurological disease modeling with patient-derived cells. Several groups, including ours, have applied the iPSC approach to model severe genetic developmental and epileptic encephalopathies (DEEs) with patient-derived cells. Although most studies to date involve 2-D cultures of patient-derived neurons, brain organoids are increasingly being employed to explore genetic DEE mechanisms. We are applying this approach to understand PMSE (Polyhydramnios,