Prognostic biomarkers of Parkinson’s disease in the Spanish EPIC cohort: a multiplatform metabolomics approach DOI Creative Commons
Carolina González-Riaño, Jorge Sáiz, Coral Barbas

et al.

npj Parkinson s Disease, Journal Year: 2021, Volume and Issue: 7(1)

Published: Aug. 16, 2021

Abstract The lack of knowledge about the onset and progression Parkinson’s disease (PD) hampers its early diagnosis treatment. Metabolomics might shed light on PD imprint seeking a broader view biochemical remodeling induced by this in an pre-symptomatic stage unveiling potential biomarkers. To achieve goal, we took advantage great European Prospective Study Nutrition Cancer (EPIC) cohort to apply metabolomics searching for diagnostic markers. This consisted healthy volunteers that were followed around 15 years until June 2011 ascertain incident PD. For untargeted metabolomics-based study, baseline preclinical plasma samples 39 randomly selected individuals developed (Pre-PD group) corresponding control group analyzed using multiplatform approach. Data statistically exposed alterations 33 metabolites levels, including significantly lower levels free fatty acids (FFAs) from subjects. These results then validated adopting targeted HPLC-QqQ-MS After integrating all affected, our finding revealed FFAs metabolism, mitochondrial dysfunction, oxidative stress, gut–brain axis dysregulation long before development hallmarks. Although biological purpose these events is still unknown, remodeled metabolic pathways highlighted work be considered worthy prognostic biomarkers prodromal findings are inestimable value since first study conducted with collected many development.

Language: Английский

Methylation across the central dogma in health and diseases: new therapeutic strategies DOI Creative Commons
Ruochen Liu, Erhu Zhao,

Huijuan Yu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 24, 2023

The proper transfer of genetic information from DNA to RNA protein is essential for cell-fate control, development, and health. Methylation DNA, RNAs, histones, non-histone proteins a reversible post-synthesis modification that finetunes gene expression function in diverse physiological processes. Aberrant methylation caused by mutations or environmental stimuli promotes various diseases accelerates aging, necessitating the development therapies correct disease-driver imbalance. In this Review, we summarize operating system across central dogma, which includes writers, erasers, readers, reader-independent outputs. We then discuss how dysregulation contributes neurological disorders, cancer, aging. Current small-molecule compounds target modifiers show modest success certain cancers. methylome-wide action lack specificity lead undesirable biological effects cytotoxicity, limiting their therapeutic application, especially with monogenic cause different directions changes. Emerging tools capable site-specific manipulation hold great promise solve dilemma. With refinement delivery vehicles, these new are well positioned advance basic research clinical translation field.

Language: Английский

Citations

56
The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing DOI Creative Commons
Yuqing Liu, Yejun Tan, Zheyu Zhang

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 23, 2024

Abstract Ageing is a crucial risk factor for Alzheimer’s disease (AD) and characterised by systemic changes in both intracellular extracellular microenvironments that affect the entire body instead of single organ. Understanding specific mechanisms underlying role ageing development can facilitate treatment ageing-related diseases, such as AD. Signs brain have been observed AD patients animal models. Alleviating pathological caused dramatically ameliorate amyloid beta- tau-induced neuropathological memory impairments, indicating plays pathophysiological process In this review, we summarize impact several age-related factors on propose preventing promising strategy improving cognitive health.

Language: Английский

Citations

33
RNA dysregulation in neurodegenerative diseases DOI Creative Commons
Yini Li, Shuying Sun

The EMBO Journal, Journal Year: 2025, Volume and Issue: 44(3), P. 613 - 638

Published: Jan. 9, 2025

Dysregulation of RNA processing has in recent years emerged as a significant contributor to neurodegeneration. The diverse mechanisms and molecular functions underlying underscore the essential role regulation maintaining neuronal health function. molecules are bound by RNA-binding proteins (RBPs), interactions between RNAs RBPs commonly affected In this review, we highlight progress understanding dysregulated RNA-processing pathways causes RBP dysfunction across various neurodegenerative diseases. We discuss both established emerging RNA-mediated neuropathogenesis rapidly evolving field. Furthermore, explore development potential RNA-targeting therapeutic approaches for treatment

Language: Английский

Citations

3
METTL3: a multifunctional regulator in diseases DOI
Na Li, Wei Xiang,

J.J. Dai

et al.

Molecular and Cellular Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Language: Английский

Citations

2
Conserved reduction of m 6 A RNA modifications during aging and neurodegeneration is linked to changes in synaptic transcripts DOI Creative Commons

Ricardo Castro-Hernández,

Tea Berulava,

Mariia Metelova

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(9)

Published: Feb. 22, 2023

N 6 -methyladenosine (m A) regulates mRNA metabolism. While it has been implicated in the development of mammalian brain and cognition, role m A synaptic plasticity, especially during cognitive decline, is not fully understood. In this study, we employed methylated RNA immunoprecipitation sequencing to obtain epitranscriptome hippocampal subregions CA1, CA3, dentate gyrus anterior cingulate cortex (ACC) young aged mice. We observed a decrease levels animals. Comparative analysis (CC) tissue from cognitively intact human subjects Alzheimer’s disease (AD) patients showed decreased methylation AD patients. changes common brains mice were found transcripts linked function including calcium/calmodulin-dependent protein kinase 2 ( CAMKII ) AMPA-selective glutamate receptor 1 Glua1 ). used proximity ligation assays show that reduced result synthesis as exemplified by GLUA1. Moreover, impaired function. Our results suggest controls may play decline associated with aging AD.

Language: Английский

Citations

43
Globally reduced N6-methyladenosine (m6A) in C9ORF72-ALS/FTD dysregulates RNA metabolism and contributes to neurodegeneration DOI
Yini Li, Xiaoyang Dou, Jun Liu

et al.

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(8), P. 1328 - 1338

Published: June 26, 2023

Language: Английский

Citations

34
Oxygen metabolism abnormality and Alzheimer's disease: An update DOI Creative Commons
Guangdong Liu, Cui Yang,

Xin Wang

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 68, P. 102955 - 102955

Published: Nov. 8, 2023

Oxygen metabolism abnormality plays a crucial role in the pathogenesis of Alzheimer's disease (AD) via several mechanisms, including hypoxia, oxidative stress, and mitochondrial dysfunction. Hypoxia condition usually results from living high-altitude habitat, cardiovascular cerebrovascular diseases, chronic obstructive sleep apnea. Chronic hypoxia has been identified as significant risk factor for AD, showing an aggravation various pathological components such amyloid β-protein (Aβ) metabolism, tau phosphorylation, dysfunction, neuroinflammation. It is known that excessive hyperoxia can both result stress Oxidative dysfunction increase Aβ proteins lead to redox imbalance, thus forming vicious cycle exacerbating AD pathology. Hyperbaric oxygen therapy (HBOT) non-invasive intervention its capacity significantly enhance cerebral oxygenation levels, which attenuate aggregation, However, further investigation imperative determine optimal pressure, duration exposure, frequency HBOT sessions. In this review, we explore prospects with aim enhancing our understanding underlying molecular mechanisms AD. Current research aimed at attenuating abnormalities holds promise providing novel therapeutic approaches

Language: Английский

Citations

28
The rise of epitranscriptomics: recent developments and future directions DOI Creative Commons

Jonas Cerneckis,

Guo‐li Ming, Hongjun Song

et al.

Trends in Pharmacological Sciences, Journal Year: 2023, Volume and Issue: 45(1), P. 24 - 38

Published: Dec. 15, 2023

The epitranscriptomics field has undergone tremendous growth since the discovery that RNA N

Language: Английский

Citations

25
Role of N6-methyladenosine modification in central nervous system diseases and related therapeutic agents DOI Creative Commons
Junya Lv, Lijuan Xing, Xin Zhong

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114583 - 114583

Published: March 28, 2023

N6-methyladenosine (m6A) is a ubiquitous mRNA modification in eukaryotes. m6A occurs through the action of methyltransferases, demethylases, and methylation-binding proteins. methylation RNA associated with various neurological disorders, including Alzheimer's disease (AD), Parkinson's (PD), depression, cerebral apoplexy, brain injury, epilepsy, arteriovenous malformations, glioma. Furthermore, recent studies report that m6A-related drugs have attracted considerable concerns therapeutic areas disorders. Here, we mainly summarized role diseases potential drugs. The aim this review expected to be useful systematically assess as new biomarker develop innovative modulators for amelioration treatment

Language: Английский

Citations

24
An Overview of Current Detection Methods for RNA Methylation DOI Open Access
Buket Sağlam, Bünyamin Akgül

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3098 - 3098

Published: March 7, 2024

Epitranscriptomic mechanisms, which constitute an important layer in post-transcriptional gene regulation, are involved numerous cellular processes under health and disease such as stem cell development or cancer. Among various RNA methylation is considered to have vital roles eukaryotes primarily due its dynamic reversible nature. There methylations that include, but not limited to, 2'-O-dimethyladenosine (m6Am), N7-methylguanosine (m7G), N6-methyladenosine (m6A) N1-methyladenosine (m1A). These biochemical modifications modulate the fate of by affecting translation, target site determination, processing, polyadenylation, splicing, structure, editing stability. Thus, it highly quantitatively measure changes marks gain insight into disease. Although there complicating challenges identifying certain genome wide, methods been developed recently facilitate quantitative measurement methylated RNAs. To this end, detection for can be classified five categories antibody-based, digestion-based, ligation-based, hybridization-based direct RNA-based methods. In review, we aimed summarize our current understanding methylation, highlighting their advantages disadvantages, along with field.

Language: Английский

Citations

16