Minimalistic in vitro systems for investigating tau pathology

Hallinan, Grace I; Pitera, Aleksandra P.; Patel, Prutha; West, Jonathan; Deinhardt, Katrin

doi:10.1016/j.jneumeth.2018.09.032

Cited by 3 publications

(2 citation statements)

References 122 publications

(143 reference statements)

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“…Tau pathology is propagated via synaptic activity (Wu et al., 2016), possibly through exosomes (Wang et al., 2017), as well as non‐synaptic mechanisms (Calafate et al., 2015). Studies using MPS have contributed to elucidate the prion‐like propagation of Tau, and to clarify tau species involved and effects on recipient cells (reviewed in (Hallinan, Pitera, et al., 2019)) and have more recently been used to screen Tau targeted prospective therapeutics. Using a three chamber MPS Nobuhara et al showed that some Tau antibodies, targeting the protein mid‐domain, efficiently blocked the Tau uptake, aggregation, and spreading (Nobuhara et al., 2017).…”

Section: Microfluidic Models Of Neurological Diseasesmentioning

confidence: 99%

Advances in microfluidic in vitro systems for neurological disease modeling

Holloway

Willaime‐Morawek

Siow

et al. 2021

J of Neuroscience Research

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Section: Microfluidic Models Of Neurological Diseasesmentioning

confidence: 99%

Advances in microfluidic in vitro systems for neurological disease modeling

Holloway

Willaime‐Morawek

Siow

et al. 2021

J of Neuroscience Research

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“…Animal can be a common source of brain cells for in vitro cultures. These cells are usually extracted from different anatomical regions of the CNS and PNS of embryos, pups or adult rodents before being seeded into compartments of microfluidic devices (Kunze et al, 2011;Seibenhener and Wooten, 2012;Southam et al, 2013;Robertson et al, 2014;Ruiz et al, 2014;Hallinan et al, 2019). Despite the advantages of using animals, this approach has some limitations.…”

Section: Cell Culture Interactions In Microfluidic Devicesmentioning

confidence: 99%

Modeling Neurodegenerative Diseases Using In Vitro Compartmentalized Microfluidic Devices

Miny

Maisonneuve²,

Quadrio

et al. 2022

Front. Bioeng. Biotechnol.

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The human brain is a complex organ composed of many different types of cells interconnected to create an organized system able to efficiently process information. Dysregulation of this delicately balanced system can lead to the development of neurological disorders, such as neurodegenerative diseases (NDD). To investigate the functionality of human brain physiology and pathophysiology, the scientific community has been generated various research models, from genetically modified animals to two- and three-dimensional cell culture for several decades. These models have, however, certain limitations that impede the precise study of pathophysiological features of neurodegeneration, thus hindering therapeutical research and drug development. Compartmentalized microfluidic devices provide in vitro minimalistic environments to accurately reproduce neural circuits allowing the characterization of the human central nervous system. Brain-on-chip (BoC) is allowing our capability to improve neurodegeneration models on the molecular and cellular mechanism aspects behind the progression of these troubles. This review aims to summarize and discuss the latest advancements of microfluidic models for the investigations of common neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis.

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Co-culture of Murine Neurons Using a Microfluidic Device for The Study of Tau Misfolding Propagation

Hallinan¹,

Lopez²,

Vargas‐Caballero³

et al. 2020

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The deposition of misfolded, aggregated tau protein is a hallmark of several neurodegenerative diseases, collectively termed "tauopathies". Tau pathology spreads throughout the brain along connected pathways in a prion-like manner. The process of tau pathology propagation across circuits is a focus of intense research and has been investigated in vivo in human post-mortem brain and in mouse models of the diseases, in vitro in diverse cellular systems including primary neurons, and in cell free assays using purified recombinant tau protein. Here we describe a protocol that takes advantage of a minimalistic neuronal circuit arrayed within a microfluidic device to follow the propagation of tau misfolding from a presynaptic to a postsynaptic neuron. This assay allows high-resolution imaging as well as individual manipulation of the releasing and receiving neuron, and is therefore beneficial for investigating the propagation of tau and other misfolded proteins in vitro.

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Minimalistic in vitro systems for investigating tau pathology

Abstract:  Misfolded tau spreads from cell to cell, and propagates in a prion-like manner.  In vitro and in vivo models exist that recapitulate aspects of tau pathology.  Microfluidic devices can recreate minimalistic, manipulatable neuronal arrays in vitro.

Cited by 3 publications

References 122 publications

Advances in microfluidic in vitro systems for neurological disease modeling

Advances in microfluidic in vitro systems for neurological disease modeling

Modeling Neurodegenerative Diseases Using In Vitro Compartmentalized Microfluidic Devices

Co-culture of Murine Neurons Using a Microfluidic Device for The Study of Tau Misfolding Propagation

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