Motor skill learning modulates striatal extracellular vesicles’ content in a mouse model of Huntington’s disease DOI Creative Commons
Júlia Solana‐Balaguer, Pol Garcia‐Segura, Genís Campoy‐Campos

и другие.

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 11, 2024

Abstract Huntington’s disease (HD) is a neurological disorder caused by CAG expansion in the Huntingtin gene ( HTT ). HD pathology mostly affects striatal medium-sized spiny neurons and results an altered cortico-striatal function. Recent studies report that motor skill learning, stimulation attenuate neuropathology HD, resulting amelioration of some cognitive functions. During physical training, extracellular vesicles (EVs) are released many tissues, including brain, as potential means for inter-tissue communication. To investigate how involving acute modulates EVs crosstalk between cells striatum, we trained wild-type (WT) R6/1 mice, latter with deficits, on accelerating rotarod test, isolated their EVs. from mice presented alterations small exosome population when compared to WT. Proteomic analyses revealed recapitulated signaling energy deficiencies present HD. Motor learning restored amount protein content comparison naïve mice. Furthermore, modulated crucial pathways metabolism neurodegeneration. All these data provide new insights into pathogenesis put spotlight understand metabolic neurodegenerative diseases. Moreover, our suggest modulator cell-to-cell communication striatum.

Язык: Английский

Salivary Huntingtin protein is uniquely associated with clinical features of Huntington’s disease DOI Creative Commons
Georgia M. Parkin, Jody Corey‐Bloom,

Chase Snell

и другие.

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Янв. 19, 2023

Abstract Measuring Huntingtin (HTT) protein in peripheral cells represents an essential step biomarker discovery for Huntington’s Disease (HD), however to date, investigations into the salivary expression of HTT has been lacking. In current study, we quantified total (tHTT) and mutant (mHTT) matched blood saliva samples using single molecule counting (SMC) immunoassays: 2B7-D7F7 2B7-MW1 (mHTT). Matched samples, clinical data, were collected from 95 subjects: n = 19 manifest HD, 34 premanifest HD (PM), 42 normal controls (NC). Total mHTT levels not correlated saliva. Plasma tHTT was significantly associated with age, participant sex; whereas CAG repeat length CAP score. did differ across cohorts. Salivary plasma increased PM compared NC; also NC. Only measures. is uniquely measures offers significant promise as a relevant, non-invasive biomarker. Its use could be immediately implemented both translational research applications.

Язык: Английский

Процитировано

12
Exosomes for the diagnosis and treatment of dementia DOI

Hyeon Su Joo,

Ha Yeong Jeon,

Eun Be Hong

и другие.

Current Opinion in Psychiatry, Год журнала: 2023, Номер 36(2), С. 119 - 125

Опубликована: Янв. 11, 2023

Dementia is a syndrome with several possible pathologies. To date, definitive methods for diagnosis and treatment of sub-types dementia have not been established. Emerging evidence suggests that exosomes can provide important information the subtypes dementia. This article reviews recent studies on application in dementia.Exosomes are involved pathogenesis Alzheimer's disease (AD) Parkinson's (PD) through transporting toxic proteins such as amyloid beta (Aβ), tau, α-synuclein. Exosomal microRNAs (miR) reflect state, therefore, be used diagnostic markers diseases AD, PD, Huntington's (HD), vascular (VaD), Lewy bodies (DLB), frontotemporal (FTD). Mesenchymal stem cell (MSC)-derived shown to ameliorate pathology, improve cognitive function VAD.Recent could novel agents because they contain molecules potential biomarker candidates indicative type stage Therapeutic has revealed only, or loaded an active pharmaceutical ingredient (API), phenotype Further work needed exploit this potential.

Язык: Английский

Процитировано

11
Extracellular vesicles as biomarker and therapeutic targets for neurological disorders DOI

Ufaq Razi,

Faizan Ahmad, Anik Karan

и другие.

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 105 - 137

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Senescence and Neurodegenerative Disorders: Beyond Alzheimer’s and Parkinson’s DOI

Isha Tiwari,

Priyanka Chauhan, Ajay Singh

и другие.

Опубликована: Янв. 1, 2025

Процитировано

0
Transcriptomic analysis of intracellular RNA granules and small extracellular vesicles: Unmasking their overlap in a cell model of Huntington’s Disease DOI Creative Commons
Deepti Kailash Nabariya,

Lisa Knüpfer,

Patrick Hartwich

и другие.

Molecular and Cellular Probes, Год журнала: 2025, Номер unknown, С. 102026 - 102026

Опубликована: Март 1, 2025

Huntington's disease (HD) arises from the abnormal expansion of a CAG repeat in HTT gene. The mutant triggers aberrant RNA-protein interactions and translates into toxic aggregate-prone polyglutamine protein. These ineractions also seed formation cytoplasmic liquid-like granules, such as stress granules. Emerging evidence demonstrates that granules formed via liquid-liquid phase separation can mature gel-like inclusions persist within cell may act precursor to aggregates occur patients' tissue. Thus, deregulation RNA is an important component neurodegeneration. Interestingly, both intracellular membrane-less organelles like secretion small extracellular vesicles (sEVs) increase upon under conditions. sEVs are lipid membrane-bound particles secreted all types participate spreading misfolded proteins complexes across central nervous system neurodegenerative diseases HD. In this study, we performed comparative transcriptomic analysis HD model. were isolated inducible Both induced non-induced (control) cells analysed by sequencing. Our between transcriptomics data showed that: (I) share content, (II) several non-coding RNAs translocate (III) composition affected cells. showing common transcripts suggest sEV loading be related. Moreover, found high abundance lncRNAs control samples, with REST regulation, highlighting their potential role pathogenesis selective incorporation sEVs. transcriptome cargo or serve source for diagnostic strategies. For example, disease-specific RNA-signatures biomarker diseases. Therefore, compared our dataset patient blood. However, cell-type specific signature sEV-secreted well variability make it difficult detect these biomarkers

Язык: Английский

Процитировано

0
Exosomes as Biomarkers and Therapeutic Agents in Neurodegenerative Diseases: Current Insights and Future Directions DOI Creative Commons

Sam Dehghani,

Ozgecan Ocakcı,

Pars Tan Hatipoglu

и другие.

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

Abstract Neurodegenerative diseases (NDs) like Alzheimer’s, Parkinson’s, and ALS rank among the most challenging global health issues, marked by substantial obstacles in early diagnosis effective treatment. Current diagnostic techniques frequently demonstrate inadequate sensitivity specificity, whilst conventional treatment strategies encounter challenges related to restricted bioavailability insufficient blood–brain barrier (BBB) permeability. Recently, exosomes—nanoscale vesicles packed with proteins, RNAs, lipids—have emerged as promising agents potential reshape therapeutic approaches these diseases. Unlike drug carriers, they naturally traverse BBB can deliver bioactive molecules affected neural cells. Their molecular cargo influence cell signaling, reduce neuroinflammation, potentially slow neurodegenerative progression. Moreover, exosomes serve non-invasive biomarkers, enabling precise while allowing real-time disease monitoring. Additionally, engineered exosomes, loaded molecules, enhance this capability targeting diseased neurons overcoming barriers. By offering enhanced reduced immunogenicity, an ability bypass physiological limitations, exosome-based present a transformative advantage over existing approaches. This review examines multifaceted role of NDDs, emphasizing their capabilities, intrinsic functions, advanced vehicles.

Язык: Английский

Процитировано

0
Overcoming biological barriers: Precision engineered extracellular vesicles for personalized neuromedicine DOI Creative Commons
V. Ravichandiran, Anuradha Kesharwani,

Anupriya

и другие.

Precision medicine and engineering., Год журнала: 2024, Номер 1(2), С. 100010 - 100010

Опубликована: Окт. 19, 2024

Язык: Английский

Процитировано

3
Challenges associated with using extracellular vesicles as biomarkers in neurodegenerative disease DOI Creative Commons
Yvonne Couch

Expert Review of Molecular Diagnostics, Год журнала: 2023, Номер 23(12), С. 1091 - 1105

Опубликована: Ноя. 2, 2023

The hunt for new biomarkers - the diagnosis of subcategories disease, or monitoring efficacy novel therapeutics is an increasingly relevant challenge in current era precision medicine. In neurodegenerative research, aim to look simple tools which can predict cognitive motor decline early, and determine whether these also be used test interventions. Extracellular vesicles (EVs) are thought play important role intercellular communication have been shown a vital number diseases.

Язык: Английский

Процитировано

7
Extracellular vesicles: biological mechanisms and emerging therapeutic opportunities in neurodegenerative diseases DOI Creative Commons
Ling Wang, Xiaoyan Zhang,

Ziyi Yang

и другие.

Translational Neurodegeneration, Год журнала: 2024, Номер 13(1)

Опубликована: Дек. 6, 2024

Abstract Extracellular vesicles (EVs) are membrane originating from different cells within the brain. The pathophysiological role of EVs in neurodegenerative diseases is progressively acknowledged. This field has advanced basic biological research to essential clinical significance. capacity selectively enrich specific subsets biofluids via distinctive surface markers opened new avenues for molecular understandings across various tissues and organs, notably In recent years, brain-derived have been extensively investigated as biomarkers, therapeutic targets, drug-delivery vehicles diseases. review provides a brief overview characteristics physiological functions classes EVs, focusing on mechanisms by which types mediate occurrence development Concurrently, novel approaches challenges use delivery delineated.

Язык: Английский

Процитировано

2
Current Diagnostic Methods and Non-Coding RNAs as Possible Biomarkers in Huntington’s Disease DOI Open Access

Miguel Pellegrini,

Guendalina Bergonzoni, Federica Perrone

и другие.

Genes, Год журнала: 2022, Номер 13(11), С. 2017 - 2017

Опубликована: Ноя. 3, 2022

Whether as a cause or symptom, RNA transcription is recurrently altered in pathologic conditions. This also true for non-coding RNAs, with regulatory functions variety of processes such differentiation, cell identity and metabolism. In line their increasingly recognized roles cellular pathways, RNAs are currently evaluated possible disease biomarkers. They could be informative not only to follow progression assess treatment efficacy clinics, but aid the development new therapeutic approaches. especially important neurological genetic disorders, where administration appropriate during prodromal stage significantly delay, if halt, progression. this review we focus on current status biomarkers Huntington’s Disease (HD), fatal hereditary degenerative condition. First, revise sources type wet use. Then, explore feasibility different types (miRNA, ncRNA, circRNA) biomarker candidates, discussing potential advantages, disadvantages, origin ongoing investigations topic.

Язык: Английский

Процитировано

8