MicroRNAs in CSF as prodromal biomarkers for Huntington disease in the PREDICT-HD study

Reed, Eric; Latourelle, Jeanne C.; Bockholt, Jeremy; Bregu, Joli; Smock, Justin; Paulsen, Jane S.; Myers, Richard H.; Investigators, Predict-Hd

doi:10.1212/wnl.0000000000004844

Cited by 70 publications

(67 citation statements)

References 31 publications

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“…First, miRNAs are particularly enriched in the mammalian brain (Nelson et al, 2008), are important in regulating neural activity (Tan et al, 2013), and could potentially serve as biomarkers for brain diseases (Reed et al, 2018). Second, the small footprint of miRNA sites facilitates packaging into virus, an important mode of gene delivery to post-mitotic neurons.…”

Section: Discussionmentioning

confidence: 99%

A MicroRNA-Based Gene-Targeting Tool for Virally Labeling Interneurons in the Rodent Cortex

Keaveney

Tseng

et al. 2018

Cell Reports

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In Brief Viral targeting of neuron subtypes is desirable for neuroscience research. Keaveney et al. developed a microRNA-based viral tool for labeling cortical interneurons. They demonstrate its utility via neuron subtype labeling in a murine disease model and in rats and through dual-color optogenetic control of two neuron types. SUMMARY More specific and broadly applicable viral gene-targeting tools for labeling neuron subtypes are needed to advance neuroscience research, especially in rodent transgenic disease models and genetically intractable species. Here, we develop a viral vector that restricts transgene expression to GABAergic interneurons in the rodent neocortex by exploiting endogenous microRNA regulation. Our interneurontargeting, microRNA-guided neuron tag, ‘‘GABA mAGNET,’’ achieves >95% interneuron selective labeling in the mouse cortex, including in a murine model of autism and also some preferential labeling of interneurons in the rat brain. We demonstrate an application of our GABA mAGNET by performing simultaneous, in vivo optogenetic control of two distinct neuron subtypes. This interneuron labeling tool highlights the potential of microRNA-based viral gene targeting to specific neuron subtypes.

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Section: Discussionmentioning

confidence: 99%

A MicroRNA-Based Gene-Targeting Tool for Virally Labeling Interneurons in the Rodent Cortex

Keaveney

Tseng

et al. 2018

Cell Reports

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“…A study by Reed et al [ 159 ] suggested that six miRNAs: miR-135b-3p, miR140-5p, miR-520f-3p, miR-8082, miR-4317 and miR-3928-5p were considerably elevated in presymptomatic HD patients, thus, representing valuable biomarkers for the early diagnosis of the disease. Another study revealed that the plasma level of miR-34b was sharply reduced in presymptomatic HD patients compared with controls, indicating that miR-34b may be a novel biomarker of HD, which can be steadily expressed in the plasma and identified before clinical symptoms [ 151 ].…”

Section: Mirna Dysregulation and Mitochondrial Dysfunction In Alzhmentioning

confidence: 99%

MicroRNAs Dysregulation and Mitochondrial Dysfunction in Neurodegenerative Diseases

Catanesi

d’Angelo

Tupone

et al. 2020

IJMS

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Neurodegenerative diseases are debilitating and currently incurable conditions causing severe cognitive and motor impairments, defined by the progressive deterioration of neuronal structure and function, eventually causing neuronal loss. Understand the molecular and cellular mechanisms underlying these disorders are essential to develop therapeutic approaches. MicroRNAs (miRNAs) are short non-coding RNAs implicated in gene expression regulation at the post-transcriptional level. Moreover, miRNAs are crucial for different processes, including cell growth, signal transmission, apoptosis, cancer and aging-related neurodegenerative diseases. Altered miRNAs levels have been associated with the formation of reactive oxygen species (ROS) and mitochondrial dysfunction. Mitochondrial dysfunction and ROS formation occur in many neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases. The crosstalk existing among oxidative stress, mitochondrial dysfunction and miRNAs dysregulation plays a pivotal role in the onset and progression of neurodegenerative diseases. Based on this evidence, in this review, with a focus on miRNAs and their role in mitochondrial dysfunction in aging-related neurodegenerative diseases, with a focus on their potential as diagnostic biomarkers and therapeutic targets.

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“…Because CSF circulates in a closed system and is in direct exchange with the brain parenchyma, it is a promising biomarker source for neurodegenerative diseases that might provide more specific insights into the cellular disease-mechanisms as compared to blood. miRNA profiles in CSF were shown to discriminate healthy controls from patients with different neurological diseases ( Dangla-Valls et al, 2017 ; Marques et al, 2017 ; Reed et al, 2018 ).…”

Section: Sources Technical Considerations and Biomarker Potential Ofmentioning

confidence: 99%

Circulating miRNAs as Diagnostic Biomarkers for Parkinson’s Disease

et al. 2018

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Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. Its main neuropathological hallmarks are the degeneration of dopaminergic neurons in the substantia nigra and alpha-synuclein containing protein inclusions, called Lewy Bodies. The diagnosis of idiopathic PD is still based on the assessment of clinical criteria, leading to an insufficient diagnostic accuracy. Additionally, there is no biomarker available allowing the prediction of the disease course or monitoring the response to therapeutic approaches. So far, protein biomarker candidates such as alpha-synuclein have failed to improve diagnosis of PD. Circulating microRNAs (miRNAs) in body fluids are promising biomarker candidates for PD, as they are easily accessible by non- or minimally-invasive procedures and changes in their expression are associated with pathophysiological processes relevant for PD. Advances in miRNA analysis methods resulted in numerous recent publications on miRNAs as putative biomarkers. Here, we discuss the applicability of different body fluids as sources for miRNA biomarkers, highlight technical aspects of miRNA analysis and give an overview on published studies investigating circulating miRNAs as biomarker candidates for diagnosis of PD and other Parkinsonian syndromes.

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MicroRNAs in CSF as prodromal biomarkers for Huntington disease in the PREDICT-HD study

Cited by 70 publications

References 31 publications

A MicroRNA-Based Gene-Targeting Tool for Virally Labeling Interneurons in the Rodent Cortex

A MicroRNA-Based Gene-Targeting Tool for Virally Labeling Interneurons in the Rodent Cortex

MicroRNAs Dysregulation and Mitochondrial Dysfunction in Neurodegenerative Diseases

Circulating miRNAs as Diagnostic Biomarkers for Parkinson’s Disease

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