Untangling the Prion-Like Misfolding Mechanism for Neurodegenerative Diseases

Sarnataro, Daniela

doi:10.20944/preprints201809.0075.v1

“…This process influences gene expression by either restricting access to promoter regions for transcription factors or affecting mRNA processing. However, DNA methylation profiles, generating epialleles (alleles differing solely by methylation), display significant heterogeneity and polymorphism due to the stochastic (as in transcription) or selective (as in gene imprinting) nature of CpG methylation [5][6][7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Brain Area-Specific Methylation Signatures Mark Patients With Schizophrenia

Morgera,

Feola,

Improda

et al. 2024

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D-Aspartate and D-Serine serve as primary agonists at glutamate receptors, playing a crucial role in modulating synaptic plasticity and cell migration within the central nervous system. The pre-cise regulation of their levels is essential and intricately linked to the expression of their synthetic and catabolic enzymes, which are, in turn, primarily influenced by epigenetic modifications. In a comprehensive analysis, we examined the methylation profiles of the promoters and transcription start sites of critical genes associated with D-Aspartate and D-Serine metabolism in human post-mortem brain tissues sourced from normal individuals and those diagnosed with schizo-phrenia. Our approach involved a qualitative method capable of identifying specific families of methylated alleles known as epialleles, sharing a common pattern of methylated non-contiguous CpGs, referred to as cores. These methylated traits exhibit stability and consistency within com-plex populations of diverse DNA-methylated molecules. Our findings reveal brain area-specific methylation signatures to the DDO, DAO and DAOA genes serving as distinctive markers that differentiate normal brain areas from those affected by schizophrenia. These methylation patterns align with the reported high D-Aspartate and low D-Serine levels observed in schizophrenic brain areas. The study suggests a potential link between epigenetic modifications and the dysreg-ulation of these neurotransmitters in schizophrenia.

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“…This process influences gene expression by either restricting access to promoter regions for transcription factors or affecting mRNA processing. However, DNA methylation profiles, generating epialleles (alleles differing solely by methylation), display significant heterogeneity and polymorphism due to the stochastic (as in transcription) or selective (as in gene imprinting) nature of CpG methylation [5][6][7][8][9][10][11][12]. 2 To address this complexity, we have developed a tool capable of identifying methylated CpGs under selection, forming a core or nucleus shared by several epialleles in linear DNA sequences [13].…”

Section: Introductionmentioning

confidence: 99%

Brain Area-Specific Methylation Signatures Mark Patients With Schizophrenia

Morgera,

Feola,

Improda

et al. 2023

Preprint

0

View full text Add to dashboard Cite

D-Aspartate and D-Serine serve as primary agonists at glutamate receptors, playing a crucial role in modulating synaptic plasticity and cell migration within the central nervous system. The pre-cise regulation of their levels is essential and intricately linked to the expression of their synthetic and catabolic enzymes, which are, in turn, primarily influenced by epigenetic modifications. In a comprehensive analysis, we examined the methylation profiles of the promoters and transcription start sites of critical genes associated with D-Aspartate and D-Serine metabolism in human post-mortem brain tissues sourced from normal individuals and those diagnosed with schizo-phrenia. Our approach involved a qualitative method capable of identifying specific families of methylated alleles known as epialleles, sharing a common pattern of methylated non-contiguous CpGs, referred to as cores. These methylated traits exhibit stability and consistency within com-plex populations of diverse DNA-methylated molecules. Our findings reveal brain area-specific methylation signatures to the DDO, DAO and DAOA genes serving as distinctive markers that differentiate normal brain areas from those affected by schizophrenia. These methylation patterns align with the reported high D-Aspartate and low D-Serine levels observed in schizophrenic brain areas. The study suggests a potential link between epigenetic modifications and the dysreg-ulation of these neurotransmitters in schizophrenia.

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Biomedical application of 2D nanomaterials in neuroscience

Li¹,

Ji²,

Liang³

et al. 2023

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Two-dimensional (2D) nanomaterials, such as graphene, black phosphorus and transition metal dichalcogenides, have attracted increasing attention in biology and biomedicine. Their high mechanical stiffness, excellent electrical conductivity, optical transparency, and biocompatibility have led to rapid advances. Neuroscience is a complex field with many challenges, such as nervous system is difficult to repair and regenerate, as well as the early diagnosis and treatment of neurological diseases are also challenged. This review mainly focuses on the application of 2D nanomaterials in neuroscience. Firstly, we introduced various types of 2D nanomaterials. Secondly, due to the repairment and regeneration of nerve is an important problem in the field of neuroscience, we summarized the studies of 2D nanomaterials applied in neural repairment and regeneration based on their unique physicochemical properties and excellent biocompatibility. We also discussed the potential of 2D nanomaterial-based synaptic devices to mimic connections among neurons in the human brain due to their low-power switching capabilities and high mobility of charge carriers. In addition, we also reviewed the potential clinical application of various 2D nanomaterials in diagnosing and treating neurodegenerative diseases, neurological system disorders, as well as glioma. Finally, we discussed the challenge and future directions of 2D nanomaterials in neuroscience. Graphical Abstract

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Untangling the Prion-Like Misfolding Mechanism for Neurodegenerative Diseases

Cited by 14 publications

References 97 publications

Brain Area-Specific Methylation Signatures Mark Patients With Schizophrenia

Brain Area-Specific Methylation Signatures Mark Patients With Schizophrenia

Brain Area-Specific Methylation Signatures Mark Patients With Schizophrenia

Biomedical application of 2D nanomaterials in neuroscience

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