Convergent molecular mechanisms underlying cognitive impairment in mucopolysaccharidosis type II

Corrêa, Thiago; Poswar, Fabiano de Oliveira; Santos-Rebouças, Cíntia Barros

doi:10.1007/s11011-021-00872-8

Cited by 2 publications

(1 citation statement)

References 71 publications

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“…For example, the formation of protein aggregates (such as amyloid depositions) and autophagy dysfunction were reported as pathological processes downstream of the GAG storage, which may severely impair cellular functions and cause further changes in the structures and/or activities of organelles and efficiencies of biochemical processes [ 123 , 124 ]. Indeed, different disturbances in cell physiology were reported in various MPS types, which significantly contribute to the disease severity [ 125 , 126 , 127 ].…”

Section: Oxtr In Mucopolysaccharidosesmentioning

confidence: 99%

Roles of the Oxytocin Receptor (OXTR) in Human Diseases

Pierzynowska

Gaffke

Żabińska

et al. 2023

IJMS

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The oxytocin receptor (OXTR), encoded by the OXTR gene, is responsible for the signal transduction after binding its ligand, oxytocin. Although this signaling is primarily involved in controlling maternal behavior, it was demonstrated that OXTR also plays a role in the development of the nervous system. Therefore, it is not a surprise that both the ligand and the receptor are involved in the modulation of behaviors, especially those related to sexual, social, and stress-induced activities. As in the case of every regulatory system, any disturbances in the structures or functions of oxytocin and OXTR may lead to the development or modulation of various diseases related to the regulated functions, which in this case include either mental problems (autism, depression, schizophrenia, obsessive-compulsive disorders) or those related to the functioning of reproductive organs (endometriosis, uterine adenomyosis, premature birth). Nevertheless, OXTR abnormalities are also connected to other diseases, including cancer, cardiac disorders, osteoporosis, and obesity. Recent reports indicated that the changes in the levels of OXTR and the formation of its aggregates may influence the course of some inherited metabolic diseases, such as mucopolysaccharidoses. In this review, the involvement of OXTR dysfunctions and OXTR polymorphisms in the development of different diseases is summarized and discussed. The analysis of published results led us to suggest that changes in OXTR expression and OXTR abundance and activity are not specific to individual diseases, but rather they influence processes (mostly related to behavioral changes) that might modulate the course of various disorders. Moreover, a possible explanation of the discrepancies in the published results of effects of the OXTR gene polymorphisms and methylation on different diseases is proposed.

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Section: Oxtr In Mucopolysaccharidosesmentioning

confidence: 99%

Roles of the Oxytocin Receptor (OXTR) in Human Diseases

Pierzynowska

Gaffke

Żabińska

et al. 2023

IJMS

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Molecular basis of neurocognitive dysfunction and psychosis in Alpha-Mannosidosis

Dewsbury,

Hargreaves,

Morgan

et al. 2024

J Transl Genet Genom

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A significant portion of patients who are afflicted with lysosomal storage diseases (LSDs) encounter neurological manifestations, including cognitive issues and developmental delay, seizures, psychiatric issues, and an overall neurodegenerative decline. In order to enhance the development of effective therapies for these symptoms, it is imperative that we allude to the neuropathophysiology that underlies these manifestations. These distinct neurological and developmental features are particularly evident in patients with Alpha-Mannosidosis (AM), a type of LSD. However, there is limited published information regarding the mechanisms and pathophysiology of these presentations in patients with this condition. Although the precise impact of lysosomal storage on the biogenesis and functioning of neuronal cells has not been clearly defined, recent studies have placed emphasis on the significance of synaptic defects influencing this dysfunction. These defects encompass changes in synaptic spines, proteins, and vesicles, as well as postsynaptic densities that potentially precipitate functional disruptions in synaptic transmission and neurodegeneration. Ultimately, this cascade is thought to result in extensive neuronal loss and, consequently, the onset of cognitive manifestations. Uncovering the effects on synaptic components in LSDs with neurological symptoms like AM will enable a better understanding of disease progression. It will also allow us to identify critical targets for therapeutic intervention and the determination of optimal time frames for targeted treatments, as well as the effects of these treatments on mitochondrial function. The available therapeutic modalities in AM are not a definitive cure for affected patients, but rather an attempt to reduce the symptomatic severity in their presentation, while aiming to regress/slow down disease progression. This review will aim to discuss and rationalize the current treatment approaches in place for AM patients in relation to their effects on the improvement of neurocognitive symptoms in affected AM individuals.

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Convergent molecular mechanisms underlying cognitive impairment in mucopolysaccharidosis type II

Cited by 2 publications

References 71 publications

Roles of the Oxytocin Receptor (OXTR) in Human Diseases

Roles of the Oxytocin Receptor (OXTR) in Human Diseases

Molecular basis of neurocognitive dysfunction and psychosis in Alpha-Mannosidosis

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