Trends in Neurosciences, Год журнала: 2023, Номер 47(2), С. 87 - 89
Опубликована: Ноя. 29, 2023
Язык: Английский
Ageing and Neurodegenerative Diseases, Год журнала: 2024, Номер 4(3)
Опубликована: Сен. 5, 2024
In recent years, transcriptomics has emerged as a key focus in neuroscience research, transcriptome modifications play significant role influencing various biological processes. N6-methyladenosine (m6A) represents dynamic and reversible form of mRNA modification prevalent eukaryotes. This is involved virtually every critical stage RNA metabolism, including stability, transcription, translation, splicing, nuclear export, decay, thereby playing pivotal normal brain development. Accumulating evidence suggests that m6A plays substantial neurodegenerative diseases, such Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS), Huntington’s (HD), while abnormal can lead to neurodevelopmental disorders. review summarizes the relationship between diseases elucidates its potential pathogenic mechanisms at molecular level.
Язык: Английский
Процитировано
1
Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 17
Опубликована: Янв. 8, 2024
The most common genetic cause of familial and sporadic amyotrophic lateral sclerosis (ALS) 19 frontotemporal dementia (FTD) is a GGGGCC hexanucleotide repeat expansion in the 20 C9orf72 gene (Balendra Isaacs, 2018), defining group neurodegenerative diseases 21 collectively referred to as c9ALS/FTD. Three pathological mechanisms have been implicated c9ALS/FTD: sense antisense RNA form foci that sequester specific RNA-23 binding proteins, impairing their normal function (Barker et al., 2017;(Swinnen 2020); 24 repeats are translated into three possible reading frames by 25 repeat-associated non-AUG-initiated (RAN) translation resulting production five 26 dipeptide proteins (DPRs), namely poly-GA, poly-GP, poly-GR, poly-PA poly-PR.Arginine-rich DPRs (poly-GR poly-PR) severe neurodegeneration Drosophila 28 (Mizielinska 2014) disrupt formation membraneless organelles, including 29 stress granules (Solomon 2021). Finally, haploinsufficiency reduced levels In particular, they highlight effect both RNA-and DPR-mediated toxicity on 77 nuclear pore complex components nucleocytoplasmic transport machinery,
Язык: Английский
Процитировано
0
Neuroscience, Год журнала: 2024, Номер unknown
Опубликована: Окт. 1, 2024
Язык: Английский
Процитировано
0
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 12987 - 12987
Опубликована: Дек. 3, 2024
The term frontotemporal dementia (FTD) comprises a group of neurodegenerative disorders characterized by the progressive degeneration frontal and temporal lobes brain with language impairment changes in cognitive, behavioral executive functions, some cases motor manifestations. A high proportion FTD are due to genetic mutations inherited an autosomal-dominant manner variable penetrance depending on implicated gene. Iron is crucial microelement that involved several cellular essential functions whole body plays additional specialized roles central nervous system (CNS) mainly through its redox-cycling properties. Such feature may be harmful under aerobic conditions, since it lead generation highly reactive hydroxyl radicals. Dysfunctions iron homeostasis CNS indeed disorders, although still challenging determine whether dyshomeostasis this but metal direct cause neurodegeneration, contributor factor or simply consequence other mechanisms. Unlike many evidence dysfunction scarce; nonetheless, recent literature intriguingly suggests possible involvement. present review aims summarize what currently known about contribution based clinical, imaging, histological, biochemical molecular studies, further suggesting new perspectives offering insights for future investigations underexplored field research.
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Дек. 17, 2024
ABSTRACT The neurodegenerative disorder Frontotemporal Dementia (FTD) can be caused by a repeat expansion (GGGGCC; G4C2) in C9orf72. function of wild-type C9orf72 and the mechanism which C9orf72-G4C2 mutation causes FTD, however, remain unresolved. Diverse disease models including human brain samples differentiated neurons from patient-derived induced pluripotent stem cells (iPSCs) identified some hallmarks associated with but these have limitations, biopsies capturing only static snapshot dynamic processes being labor-intensive, costly, post-mitotic. We find that iPSCs, without into neurons, exhibit established FTD hallmarks, increased lysosome pH, decreased lysosomal cathepsin activity, cytosolic TDP-43 proteinopathy, nuclear TFEB. Moreover, lowering pH iPSCs mitigates suggesting key role for dysfunction. RNA-seq reveals dysregulated transcripts affecting calcium signaling, cell death, synaptic function, neuronal development. confirm differences protein expression genes not previously linked to CNTFR (neuronal survival), Annexin A2 (anti-apoptotic), NANOG development), moesin (cytoskeletal dynamics). Our findings underscore potential as model studying cellular pathology drug screening identify therapeutics. SIGNIFICANCE STATEMENT Understanding GGGGCC gene remains challenge. This study shows undifferentiated hallmark characteristics, dysfunction identifies related neurodegeneration. These highlight valuable screening, potentially guiding future research therapeutic
Язык: Английский
Процитировано
0
Cell Reports, Год журнала: 2024, Номер 44(1), С. 115107 - 115107
Опубликована: Дек. 21, 2024
Язык: Английский
Процитировано
0
Neural Regeneration Research, Год журнала: 2024, Номер 20(11), С. 3217 - 3218
Опубликована: Окт. 22, 2024
Язык: Английский
Процитировано
0
Trends in Neurosciences, Год журнала: 2023, Номер 47(2), С. 87 - 89
Опубликована: Ноя. 29, 2023
Язык: Английский
Процитировано
0