Peripheral Biomarkers in Manifest and Premanifest Huntington’s Disease

Morena, Emanuele; Romano, Carmela; Marconi, Martina; Diamant, Selene; Buscarinu, Maria Chiara; Bellucci, Gianmarco; Romano, Silvia; Scarabino, Daniela; Salvetti, Marco; Ristori, Giovanni

doi:10.3390/ijms24076051

Cited by 12 publications

(8 citation statements)

References 97 publications

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“…In recent years, emerging studies suggest that mechanisms underlying many neurodegenerative diseases extend beyond the brain [ 57 , 58 , 59 , 60 , 61 ]. This includes phenomena such as protein aggregation and mitochondrial dysfunction in peripheral organs, alterations in peripheral metabolism, and peripheral inflammation.…”

Section: Discussionmentioning

confidence: 99%

Intravenous MSC-Treatment Improves Impaired Brain Functions in the R6/2 Mouse Model of Huntington’s Disease via Recovered Hepatic Pathological Changes

Yu-Taeger,

El-Ayoubi,

et al. 2024

Cells

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Huntington’s disease (HD), a congenital neurodegenerative disorder, extends its pathological damages beyond the nervous system. The systematic manifestation of HD has been extensively described in numerous studies, including dysfunction in peripheral organs and peripheral inflammation. Gut dysbiosis and the gut–liver–brain axis have garnered greater emphasis in neurodegenerative research, and increased plasma levels of pro-inflammatory cytokines have been identified in HD patients and various in vivo models, correlating with disease progression. In the present study, we investigated hepatic pathological markers in the liver of R6/2 mice which convey exon 1 of the human mutant huntingtin gene. Furthermore, we evaluated the impact of intravenously administered Mesenchymal Stromal Cells (MSCs) on the liver enzymes, changes in hepatic inflammatory markers, as well as brain pathology and behavioral deficits in R6/2 mice. Our results revealed altered enzyme expression and increased levels of inflammatory mediators in the liver of R6/2 mice, which were significantly attenuated in the MSC-treated R6/2 mice. Remarkably, neuronal pathology and altered motor activities in the MSC-treated R6/2 mice were significantly ameliorated, despite the absence of MSCs in the postmortem brain. Our data highlight the importance of hepatic pathological changes in HD, providing a potential therapeutic approach. Moreover, the data open new perspectives for the search in blood biomarkers correlating with liver pathology in HD.

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Section: Discussionmentioning

confidence: 99%

Intravenous MSC-Treatment Improves Impaired Brain Functions in the R6/2 Mouse Model of Huntington’s Disease via Recovered Hepatic Pathological Changes

Yu-Taeger,

El-Ayoubi,

et al. 2024

Cells

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“…In addition to mHTT, several potential biomarkers have been evaluated, such as S100 calcium-binding protein B (S100B), NfL, and tau protein. However, many of these molecules have not shown significant differences between HD patients and healthy controls and did not correlate with disease severity [110,111].…”

Section: Huntington's Diseasementioning

confidence: 99%

Molecular Biomarkers of Neurodegenerative Disorders: A Practical Guide to Their Appropriate Use and Interpretation in Clinical Practice

Agnello,

Gambino,

Ciaccio

et al. 2024

IJMS

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Neurodegenerative disorders (NDs) represent a group of different diseases characterized by the progressive degeneration and death of the nervous system’s cells. The diagnosis is challenging, especially in the early stages, due to no specific clinical signs and symptoms. In this context, laboratory medicine could support clinicians in detecting and differentiating NDs. Indeed, biomarkers could indicate the pathological mechanisms underpinning NDs. The ideal biofluid for detecting the biomarkers of NDs is cerebrospinal fluid (CSF), which has limitations, hampering its widespread use in clinical practice. However, intensive efforts are underway to introduce high-sensitivity analytical methods to detect ND biomarkers in alternative nonivasive biofluid, such as blood or saliva. This study presents an overview of the ND molecular biomarkers currently used in clinical practice. For some diseases, such as Alzheimer’s disease or multiple sclerosis, biomarkers are well established and recommended by guidelines. However, for most NDs, intensive research is ongoing to identify reliable and specific biomarkers, and no consensus has yet been achieved.

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“…Longitudinal study of such individuals has identified a number of early symptoms, including autonomic symptoms [ 30 ] and neuropsychiatric symptoms including depression, apathy, irritability and altered executive function [ 31 , 32 ]. Early investigation into biomarkers in HD suggests a promising role for serum neurofilament light protein; this has been shown to correlate with clinical and radiological changes in HD [ 33 ].…”

Section: Lessons From Other Diseasesmentioning

confidence: 99%

Prodromal multiple sclerosis: considerations and future utility

Harding,

Kreft,

Ben-Shlomo

et al. 2024

J Neurol

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A multiple sclerosis (MS) prodrome has recently been described and is characterised by increased rates of healthcare utilisation and an excess frequency of fatigue, bladder problems, sensory symptoms and pain, in the years leading up to clinical onset of disease. This important observation may have several potential applications including in the identification of risk factors for disease, the potential to delay or prevent disease onset and early opportunities to alter disease course. It may also offer possibilities for the use of risk stratification algorithms and effective population screening. If standardised, clearly defined and disease specific, an MS prodrome is also likely to have a profound influence on research and clinical trials directed at the earliest stages of disease. In order to achieve these goals, it is essential to consider experience already gleaned from other disorders. More specifically, in some chronic neurological disorders the understanding of disease pro-drome is now well advanced and has been successfully applied. However, understanding of the MS prodrome remains at an early stage with key questions including the length of the prodrome, symptom specificity and potential benefits of early intervention as yet unanswered. In this review we will explore the evidence available to date and suggest future research strategies to address unanswered questions. In addition, whilst current understanding of the MS prodrome is not yet sufficient to justify changes in public health policy or MS management, we will consider the practical utility and future application of the MS prodrome in a wider health care setting.

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Peripheral Biomarkers in Manifest and Premanifest Huntington’s Disease

Cited by 12 publications

References 97 publications

Intravenous MSC-Treatment Improves Impaired Brain Functions in the R6/2 Mouse Model of Huntington’s Disease via Recovered Hepatic Pathological Changes

Intravenous MSC-Treatment Improves Impaired Brain Functions in the R6/2 Mouse Model of Huntington’s Disease via Recovered Hepatic Pathological Changes

Molecular Biomarkers of Neurodegenerative Disorders: A Practical Guide to Their Appropriate Use and Interpretation in Clinical Practice

Prodromal multiple sclerosis: considerations and future utility

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