Elsevier eBooks, Год журнала: 2024, Номер unknown, С. 309 - 340
Опубликована: Ноя. 29, 2024
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(8), С. 4323 - 4323
Опубликована: Апрель 13, 2024
Neurodegenerative disorders (NDs) represent a group of different diseases characterized by the progressive degeneration and death nervous system's cells. The diagnosis is challenging, especially in early stages, due to no specific clinical signs symptoms. In this context, laboratory medicine could support clinicians detecting differentiating NDs. Indeed, biomarkers indicate pathological mechanisms underpinning ideal biofluid for NDs cerebrospinal fluid (CSF), which has limitations, hampering its widespread use practice. However, intensive efforts are underway introduce high-sensitivity analytical methods detect ND alternative nonivasive biofluid, such as blood or saliva. This study presents an overview molecular currently used For some diseases, Alzheimer's disease multiple sclerosis, well established recommended guidelines. most NDs, research ongoing identify reliable biomarkers, consensus yet been achieved.
Язык: Английский
Процитировано
9
Journal of Movement Disorders, Год журнала: 2024, Номер 17(2), С. 181 - 188
Опубликована: Фев. 21, 2024
Huntington's disease (HD) is an autosomal dominant, fully penetrant, neurodegenerative that most commonly affects middle-aged adults. HD caused by a CAG repeat expansion in the HTT gene, resulting expression of mutant huntingtin (mHTT). Our aim was to detect and quantify mHTT tear fluid, which, our knowledge, has never been measured before.
Язык: Английский
Процитировано
5
Frontiers in Molecular Neuroscience, Год журнала: 2025, Номер 17
Опубликована: Янв. 10, 2025
To further advance our understanding of Muscular Dystrophies (MDs) and Spinocerebellar Ataxias (SCAs), it is necessary to identify the biological patterns associated with disease pathology. Although progress has been made in fields genetics transcriptomics, there a need for proteomics metabolomics studies. The present study aimed be first document serum metabolic signatures MDs (DMD, BMD, LGMD 2A) SCAs (SCA 1-3), from South Asian perspective. A total 28 patients 1-10, SCA 2-2, 3-2, DMD-10, BMD-2, LGMD-2) eight controls (aged 8-65 years) were included. Metabolomic analysis was performed by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS), support Houston Omics Collaborative. Amino acid metabolism primary altered super pathway DMD followed carbohydrate lipid metabolism. In contrast, BMD 2A exhibited more prominent alteration amino SCAs, primarily lipid, acid, peptide, nucleotide, xenobiotics pathways are affected. Our findings offer new insights into variance metabolite levels MD SCA, substantial implications pathology, drug development, therapeutic targets clinical management. Intriguingly, this identified two novel metabolites SCA. This pilot cross-sectional warrants research involving larger groups participants, validate findings.
Язык: Английский
Процитировано
0
Biology, Год журнала: 2025, Номер 14(2), С. 129 - 129
Опубликована: Янв. 26, 2025
Neurodegenerative disorders (NDs) cause progressive neuronal loss and are a significant public health concern, with NDs projected to become the second leading global of death within two decades. Huntington’s disease (HD) is rare, ND caused by an autosomal-dominant mutation in huntingtin (HTT) gene, severe brain resulting debilitating motor, cognitive, psychiatric symptoms. Given complex pathology HD, biomarkers essential for performing early diagnosis, monitoring progression, evaluating treatment efficacy. However, identification consistent HD challenging due prolonged premanifest stage, HD’s heterogeneous presentation, its multiple underlying biological pathways. This study involves 10-year bibliometric analysis biomarker research, revealing key research trends gaps. The also features comprehensive literature review emerging biomarkers, concluding need better stratification patients well-designed longitudinal studies validate biomarkers. Promising candidate wet biomarkers— including neurofilament light chain protein (NfL), microRNAs, mutant HTT protein, specific metabolic inflammatory markers— discussed, emphasis on their potential utility stage. Additionally, reflecting structural deficits motor or behavioral impairments, such as neurophysiological (e.g., tapping, speech, EEG, event-related potentials) imaging MRI, PET, diffusion tensor imaging) evaluated. findings underscore that discovery validation reliable urgently require improved patient studies. Reliable particularly crucial optimizing clinical management strategies, enabling personalized approaches, advancing trials HD-modifying therapies.
Язык: Английский
Процитировано
0
Innovare Journal of Medical Sciences, Год журнала: 2025, Номер unknown, С. 6 - 13
Опубликована: Янв. 1, 2025
A rare genetic neurodegenerative disorder called Huntington’s disease (HD) causes nerve cells to progressively die. When the trinucleotide CAG repeats are <36, it is regarded as “normal.” repetitions in huntingtin gene >36, polyglutamine (polyQ) tract leads polyQ poisoning, which turn psychological, genetic, and movement disorders hallmarks of HD. One particularly concerning aspect HD its controlling inheritance pattern, this indicates that each child born a parent who exaggerated through condition has 50% likelihood having lineage mutated disease. As result, there significant risk offspring individuals with may also develop condition. The underlying molecular mechanisms resulting visible loss neurons remain incompletely elucidated, current therapeutic approaches primarily aim alleviate symptoms. Many symptoms can be treated prescription medications currently available. These include prescribed medication for chorea, tranquilizers, calming agents, antidepressants, non-pharmacological therapy. Additional possible treatments now undergoing clinical research RNA interference therapies, therapies targeting using tiny molecules, antibody stem cell small molecule not RNA, concentrating on neuroinflammation. Among potential presently pre-clinical development stages zinc-finger protein transcription activator-like effector nuclease rehabilitations involving clustered regularly interspaced short palindromic (CRISPS)/CRISPS-associated system. Therefore, purpose comprehensive review discuss efficacy medicines look into insights new emerging under stage.
Язык: Английский
Процитировано
0
Journal of Neurology, Год журнала: 2025, Номер 272(3)
Опубликована: Март 1, 2025
Tau is a microtubule protein that known to be hyperphosphorylated and aggregate in several chronic neurodegenerative disorders. In many cases, particular Alzheimer's disease, the degree of tau pathology has been demonstrated correlate with cognitive deficits and/or decline. Huntington's disease (HD), dominantly inherited disorder, both impairments abnormal expression have reported occur, along accumulation mutant huntingtin protein. this respect, shown present cerebrospinal fluid individuals HD increase progression. However, how relates changes found periphery largely unknown. study, we collected blood samples from patients isolated multiple components including plasma, platelets, peripheral mononuclear cells measure their levels subsequently these stage. Our results suggest amount tau, particularly N-terminal (NTA-tau) total (t-tau), elevated all assayed quantity within specifically, strongly correlated severity.
Язык: Английский
Процитировано
0
Pharmaceuticals, Год журнала: 2023, Номер 16(12), С. 1714 - 1714
Опубликована: Дек. 11, 2023
Metformin, a widely prescribed medication for type 2 diabetes, has garnered increasing attention its potential neuroprotective properties due to the growing demand treatments Alzheimer's, Parkinson's, and motor neuron diseases. This review synthesizes experimental clinical studies on metformin's mechanisms of action therapeutic benefits neurodegenerative disorders. A comprehensive search electronic databases, including PubMed, MEDLINE, Embase, Cochrane library, focused key phrases such as "metformin", "neuroprotection", "neurodegenerative diseases", with data up September 2023. Recent research glucoregulatory reveals new molecular targets, activation LKB1-AMPK signaling pathway, which is crucial chronic administration metformin. The pleiotropic impact may involve other stress kinases that are acutely activated. precise role respiratory chain complexes (I IV), mitochondrial or lysosomes in metformin effects remains be established by further research. Research extrahepatic targets like gut microbiota, well antioxidant immunomodulatory properties, understanding Experimental animal models shows promising results, but inconclusive. Understanding could help design trials explore and, hopefully, prove conditions.
Язык: Английский
Процитировано
10
Ageing and Neurodegenerative Diseases, Год журнала: 2024, Номер 4(1)
Опубликована: Янв. 19, 2024
Telomeres, essential DNA-protein complexes located at chromosome ends, play a critical role in preventing fusion, recombination, and degradation, thus ensuring genomic stability. When telomeres reach limiting shortened length, they will activate DNA damage checkpoints, stop cell division trigger replicative senescence. Telomerase is composed of RNA protein, which can synthesize repeat sequences, elongate telomeres. Studies have shown that telomere length (TL) telomerase activity are closely involved aging, aging-related degenerative diseases, tumors. Neurodegenerative diseases (NDDs) one the major caused by both genetic environmental factors, characterized insidious onset, difficult diagnosis, irreversible disease progression, lack effective treatments, brings heavy burden to society families. Currently, many studies noted variations leukocyte (LTL) NDDs, suggesting vital for NDD pathogenesis. This review explores relationship between TL examines as potential therapeutic target, discusses emerging biomarkers intervention strategies diagnosis treatment.
Язык: Английский
Процитировано
2
Journal of Neurorestoratology, Год журнала: 2024, Номер unknown, С. 100176 - 100176
Опубликована: Дек. 1, 2024
Язык: Английский
Процитировано
2
Metabolites, Год журнала: 2023, Номер 13(12), С. 1203 - 1203
Опубликована: Дек. 18, 2023
Huntington’s disease (HD) is a progressive, fatal neurodegenerative characterized by motor, cognitive, and psychiatric symptoms. The precise mechanisms of HD progression are poorly understood; however, it known that there an expansion the trinucleotide cytosine-adenine-guanine (CAG) repeat in Huntingtin gene. Important new strategies paramount importance to identify early biomarkers with predictive value for intervening at stage when cellular dysfunction has not progressed irreversibly. Metabolomics study global metabolite profiles system (cell, tissue, or organism) under certain conditions becoming essential tool systemic characterization metabolites provide snapshot functional pathophysiological states organism support diagnosis biomarker discovery. This review briefly highlights historical progress metabolomic methodologies, followed more detailed use metabolomics research enable greater understanding pathogenesis, its prediction, finally main technical platforms field metabolomics.
Язык: Английский
Процитировано
4