Molecular Mechanisms of Rett Syndrome: Emphasizing the Roles of Monoamine, Immunity, and Mitochondrial Dysfunction DOI Creative Commons

Júlia Lopes Gonçalez,

Jenny Shen,

Wei Li

и другие.

Cells, Год журнала: 2024, Номер 13(24), С. 2077 - 2077

Опубликована: Дек. 17, 2024

Rett syndrome (RTT), which predominantly affects females, arises in most cases from mutations the Methyl-CpG-binding Protein-2 (MECP2) gene. When MeCP2 is impaired, it disrupts regulation of numerous genes, causing production dysfunctional proteins associated with various multi-systemic issues RTT. In this review, we explore current insights into molecular signaling related to monoamines, immune response, and mitochondrial function, their implications for pathophysiology Research has shown that monoamines—such as dopamine, norepinephrine, epinephrine, serotonin, histamine—exhibit alterations RTT, contributing a range neurological symptoms. Furthermore, system RTT individuals demonstrates dysfunction through abnormal activity microglia, macrophages, lymphocytes, non-immune cells, leading atypical release inflammatory mediators disruptions NF-κB pathway. Moreover, mitochondria, essential energy calcium storage, also show condition. The delicate balance producing scavenging reactive oxygen species—termed redox balance—is disrupted Targeting these pathways presents promising avenue developing effective therapies.

Язык: Английский

Neural precursor cells rescue symptoms of Rett syndrome by activation of the Interferon γ pathway DOI Creative Commons
Angelisa Frasca, Federica Miramondi, Erica Butti

и другие.

EMBO Molecular Medicine, Год журнала: 2024, Номер 16(12), С. 3218 - 3246

Опубликована: Сен. 20, 2024

The beneficial effects of Neural Precursor Cell (NPC) transplantation in several neurological disorders are well established and they generally mediated by the secretion immunomodulatory neurotrophic molecules. We therefore investigated whether Rett syndrome (RTT), that represents first cause severe intellectual disability girls, might benefit from NPC-based therapy. Using vitro co-cultures, we demonstrate that, sensing pathological context, NPC-secreted factors induce recovery morphological synaptic defects typical Mecp2 deficient neurons. In vivo, prove intracerebral NPCs RTT mice significantly ameliorates functions. To uncover molecular mechanisms underpinning benefic effects, analyzed transcriptional profile cerebellum transplanted animals, disclosing possible involvement Interferon γ (IFNγ) pathway. Accordingly, report capacity IFNγ to rescue defects, as motor cognitive alterations models, thereby suggesting this pathway a potential therapeutic target for RTT.

Язык: Английский

Процитировано

4
BIOCHEMICAL AND MOLECULAR DETERMINANTS OF THE SUBCLINICAL INFLAMMATORY MECHANISMS IN RETT SYNDROME DOI Creative Commons
Valeria Cordone

Archives of Biochemistry and Biophysics, Год журнала: 2024, Номер 757, С. 110046 - 110046

Опубликована: Май 28, 2024

To date, Rett syndrome (RTT), a genetic disorder mainly caused by mutations in the X-linked MECP2 gene, is increasingly considered broad-spectrum pathology, instead of just neurodevelopmental disease, due to multitude peripheral co-morbidities and compromised metabolic pathways, affecting patients. The altered molecular processes include an impaired mitochondrial function, perturbed redox homeostasis, chronic subclinical inflammation improper cholesterol metabolism. persistent inflammatory condition was first defined ten years ago, as previously unrecognized feature RTT, playing role pathology progress modulation phenotypical severity. In light this, present work aims at reviewing current knowledge on status immune/inflammatory functions well investigating emerging mechanisms underlying this with special focus latest findings about inflammasome system, autoimmunity responses intestinal micro- mycobiota. On these bases, although further research needed, future therapeutic strategies able re-establish adequate response could represent potential approaches for RTT

Язык: Английский

Процитировано

3
A novel approach to metabolic profiling in case models of MECP2-related disorders DOI Creative Commons
Jessica A. Cooley Coleman, Bridgette A. Moffitt, William C. Bridges

и другие.

Metabolic Brain Disease, Год журнала: 2025, Номер 40(2)

Опубликована: Фев. 13, 2025

Abstract Genetic abnormalities of the MECP2 gene cause several conditions grouped under umbrella term -related disorders and characterized by a variety phenotypes. We applied functional approach to identify metabolic profiles in two patients with Rett syndrome (RTT) one patient duplication (MRXSL). Such an is based on Phenotype Mammalian Microarray (PM-M) technology, which designed assess cellular production energy presence different compounds generating distinct environments. The findings three case models were compared versus 50 controls. Although small number samples prevented most results from reaching significant p -values when adjusted Benjamini-Hochberg correction, some interesting trends emerged. Some indicated shared conditions, like increased sources such as pectin, adenosine, pyruvic acid, or decreased response certain hormones. Other showed opposite for disorders, interleukin-1 beta (IL-1 beta), caused RTT group but MRXSL. IL-1 also offers valuable insights into pathogenic mechanism potential therapeutic approaches. profiling bears remarkable translational since it may be helpful investigate molecular underlying phenotypical this spectrum develop biomarkers identification ideal candidates treatments recently approved trofenatide, targets development novel

Язык: Английский

Процитировано

0
Exploring the complexity of MECP2 function in Rett syndrome DOI
Yi Liu, Troy W. Whitfield, George W. Bell

и другие.

Nature reviews. Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Май 13, 2025

Язык: Английский

Процитировано

0
Interpreting the rich dialogue between astrocytes and neurons: An overview in Rett syndrome DOI Creative Commons

Francesca Maddalena Postogna,

Ottavia Maria Roggero, Fabio Biella

и другие.

Brain Research Bulletin, Год журнала: 2025, Номер 227, С. 111386 - 111386

Опубликована: Май 15, 2025

Язык: Английский

Процитировано

0
GM1 Oligosaccharide Ameliorates Rett Syndrome Phenotypes In Vitro and In Vivo via Trk Receptor Activation DOI Open Access
Maria Fazzari, Giulia Lunghi, Emma Veronica Carsana

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(21), С. 11555 - 11555

Опубликована: Окт. 28, 2024

Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. Despite advancements research, no cure exists due to an incomplete understanding of molecular effects MeCP2 deficiency. Previous studies have identified impaired tropomyosin receptor kinase (Trk) neurotrophin (NTP) signaling and mitochondrial redox imbalances as key drivers pathology. Moreover, altered glycosphingolipid metabolism has been reported RTT. GM1 ganglioside known regulator nervous system, growing evidence indicates its importance maintaining neuronal homeostasis via oligosaccharide chain, coded GM1-OS. GM1-OS directly interacts with Trk receptors on cell surface, triggering neurotrophic neuroprotective pathways neurons. In this study, we demonstrate that ameliorates RTT deficits Mecp2-null model. restored synaptogenesis reduced oxidative stress Mecp2-knock-out (ko) cortical When administered vivo, mitigated RTT-like symptoms. Our findings indicate were mediated activation neuron’s plasma membrane. Overall, our results highlight promising candidate for treatment.

Язык: Английский

Процитировано

1
Molecular Mechanisms of Rett Syndrome: Emphasizing the Roles of Monoamine, Immunity, and Mitochondrial Dysfunction DOI Creative Commons

Júlia Lopes Gonçalez,

Jenny Shen,

Wei Li

и другие.

Cells, Год журнала: 2024, Номер 13(24), С. 2077 - 2077

Опубликована: Дек. 17, 2024

Rett syndrome (RTT), which predominantly affects females, arises in most cases from mutations the Methyl-CpG-binding Protein-2 (MECP2) gene. When MeCP2 is impaired, it disrupts regulation of numerous genes, causing production dysfunctional proteins associated with various multi-systemic issues RTT. In this review, we explore current insights into molecular signaling related to monoamines, immune response, and mitochondrial function, their implications for pathophysiology Research has shown that monoamines—such as dopamine, norepinephrine, epinephrine, serotonin, histamine—exhibit alterations RTT, contributing a range neurological symptoms. Furthermore, system RTT individuals demonstrates dysfunction through abnormal activity microglia, macrophages, lymphocytes, non-immune cells, leading atypical release inflammatory mediators disruptions NF-κB pathway. Moreover, mitochondria, essential energy calcium storage, also show condition. The delicate balance producing scavenging reactive oxygen species—termed redox balance—is disrupted Targeting these pathways presents promising avenue developing effective therapies.

Язык: Английский

Процитировано

1