GeroScience, Год журнала: 2024, Номер unknown
Опубликована: Сен. 23, 2024
Язык: Английский
Metabolites, Год журнала: 2025, Номер 15(1), С. 10 - 10
Опубликована: Янв. 2, 2025
Huntington's disease (HD) is a multifaceted neurological disorder characterized by the progressive deterioration of motor, cognitive, and psychiatric functions. Despite limited understanding its pathogenesis, research has implicated abnormal trinucleotide cytosine-adenine-guanine CAG repeat expansion in huntingtin gene (HTT) as critical factor. The development innovative strategies imperative for early detection predictive biomarkers, enabling timely intervention mitigating irreversible cellular damage. Lipidomics, comprehensive analytical approach, emerged an indispensable tool systematically characterizing lipid profiles elucidating their role pathology. A MedLine search was performed to identify studies that use lipidomics characterization HD. Search terms included "Huntington disease"; "lipidomics"; "biomarker discovery"; "NMR"; "Mass spectrometry". This review highlights significance HD diagnosis treatment, exploring changes brain lipids Recent breakthroughs techniques, particularly mass spectrometry NMR spectroscopy, have revolutionized research, researchers gain deeper insights into complex lipidome brain. broad spectrum alterations vital precise diagnostic evaluation effective management. integration with artificial intelligence interdisciplinary collaboration holds promise addressing clinical variability
Язык: Английский
Процитировано
1
Lipids in Health and Disease, Год журнала: 2025, Номер 24(1)
Опубликована: Фев. 8, 2025
The liver‒brain axis is critical in neurodegenerative diseases (NDs), with lipid metabolism influencing neuroinflammation and microglial function. A systematic investigation of the genetic relationship between abnormalities ND, namely, Alzheimer's disease (AD), Parkinson's (PD), multiple sclerosis (MS), amyotrophic lateral (ALS), lacking. To assess potential causal links ND six parameters, two-sample Mendelian randomization (MR) was used. Large-scale European ancestry GWAS data for parameters (AD, ALS, PD, MS) were Genetic variants demonstrating significant correlations (P < 5 × 10-8) identified employed as instrumental variables (IVs) after proper validation. research incorporated UK Biobank genomic to examine associations parameters. analysis included primary MR, sensitivity analyses, multivariable which considered mediators. MR via inverse-variance weighted method revealed effects cholesterol (CHOL, OR = 1.10, 95% CI: 1.03-1.18, P 4.23 10⁻3) low-density lipoprotein (LDLC, 1.03-1.17, 3.28 on risk validated across methods. Potential observed ApoB ALS inversely correlated AD, whereas no found PD or MS. CHOL LDLC demonstrated heterogeneity pleiotropy, supporting their reliability. Higher levels associated increased risk, suggesting a link, hypothesis ND. Current evidence does not support role MS etiology, other NDs may be more complex warrants further investigation.
Язык: Английский
Процитировано
1
CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(10)
Опубликована: Окт. 1, 2024
Huntington's disease (HD) is a devastating neurodegenerative that manifested by gradual loss of physical, cognitive, and mental abilities. As the advances, age has major impact on pathogenic signature mutant huntingtin (mHTT) protein aggregation. This review aims to explore intricate relationship between aging, mHTT toxicity, cellular senescence in HD. Scientific data interplay mHTT, HD were collected from several academic databases, including PubMed, Google Scholar, Google, ScienceDirect. The search terms employed "AGING," "HUNTINGTON'S DISEASE," "MUTANT HUNTINGTIN," "CELLULAR SENESCENCE." Additionally, gather information molecular mechanisms potential therapeutic targets, was extended include relevant such as "DNA DAMAGE," "OXIDATIVE STRESS," "AUTOPHAGY." According research, aging leads worsening pathophysiology through some processes. result accumulation, promoted, which causes DNA damage, oxidative stress, decreased autophagy, increased inflammatory responses. Pro-inflammatory cytokines other substances are released senescent cells, may worsen neuronal damage course disease. It been shown treatments directed at these pathways reduce symptoms enhance longevity experimental animals, pointing new possibility treating condition. Through their amplification harmful effects play crucial roles development Comprehending interplays creates novel opportunities for measures targeted alleviating enhancing patients' quality life.
Язык: Английский
Процитировано
6
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Ноя. 4, 2024
Abstract Huntington’s disease (HD) arises from a CAG expansion in the huntingtin ( HTT ) gene beyond critical threshold. A major thrust of current HD therapeutic development is lowering levels mutant mRNA (m and protein (mHTT) with aim reducing toxicity these product(s). Human genetic data also support key role for somatic instability (SI) ’s repeat – whereby it lengthens age specific cell types as driver motor dysfunction onset. Thus, an attractive therapy would address both mHTT SI, but to date relationship between SI remains unexplored. Here, we investigated multiple therapeutically-relevant HTT-lowering modalities establish knock-in mice. We find that repressing transcription Htt provides robust protection using diverse pharmacological approaches (antisense oligonucleotides, CRISPR-Cas9 genome editing, Lac repressor, virally delivered zinc finger transcriptional repressor proteins, ZFPs). However, small interfering RNA (siRNA), potent treatment, lowers without influencing normal mice lacking 50% total levels, suggesting per se , do not modulate trans . Remarkably, modified ZFPs bind m locus, lack repressive domain, robustly protect despite or levels. These results have important implications HD, they suggest DNA-targeted treatments may significant advantages compared other approaches, interaction DNA-binding HTT’ s repeats provide while sparing expression.
Язык: Английский
Процитировано
2
Neuroscience and Behavioral Physiology, Год журнала: 2024, Номер 54(7), С. 1042 - 1060
Опубликована: Авг. 27, 2024
Язык: Английский
Процитировано
1
GeroScience, Год журнала: 2024, Номер unknown
Опубликована: Сен. 23, 2024
Язык: Английский
Процитировано
0