Using induced pluripotent stem cell neuronal models to study neurodegenerative diseases

Zhang, Xinwen; Hu, Di; Shang, Yutong; Qi, Xin

doi:10.1016/j.bbadis.2019.03.004

Cited by 28 publications

(27 citation statements)

References 167 publications

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“…Neurons derived from human iPSCs maintain endogenous expression of disease associated genes and proteins rather than relying on overexpression in non-human animal models. However, many previous iPSC differentiation protocols take months to generate spinal neurons leading to increased differentiation and batch variability Zhang et al, 2019a). To model C9orf72 ALS with iPSCs, spinal neurons were differentiated using the direct induced motor neuron (diMNs) protocol ( Fig.…”

Section: Characterization Of C9orf72 Pathology In An Accelerated Ipscmentioning

confidence: 99%

G₄C₂repeat RNA mediates the disassembly of the nuclear pore complex in C9orf72 ALS/FTD

Coyne

Zaepfel

Hayes

et al. 2020

Preprint

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Nucleocytoplasmic transport, controlled by the nuclear pore complex, has recently emerged as a pathomechanism underlying neurodegenerative diseases including C9orf72 ALS/FTD. However, little is known about the underlying molecular events and the underlying biology in human neurons. Using super resolution structured illumination microscopy of twenty three nucleoporins in nuclei from C9orf72 iPSC derived neurons and postmortem human tissue we identify a unique subset of eight nucleoporins lost from human neuronal nuclei. POM121, an integral transmembrane nucleoporin, appears to coordinate the composition of the nucleoporins within human neuronal nuclei ultimately impacting nucleocytoplasmic transport, and subsequent cellular toxicity in C9orf72 iPSNs. These data suggest that POM121 is a critical nucleoporin in the maintenance of the nuclear localization of specific nucleoporins in human neurons. Moreover, loss of nuclear POM121, as a result of expanded C9orf72 ALS/FTD repeat RNA, initiates a pathological cascade affecting nucleoporin composition within neuronal nuclei, nuclear pore complex function, and overall downstream neuronal survival.

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Section: Characterization Of C9orf72 Pathology In An Accelerated Ipscmentioning

confidence: 99%

G₄C₂repeat RNA mediates the disassembly of the nuclear pore complex in C9orf72 ALS/FTD

Coyne

Zaepfel

Hayes

et al. 2020

Preprint

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“…In fact, neurons differentiated from patient-specific iPSCs harboring genetic variants in PS1 and PS2 showed impaired neurite outgrowth and increased Aβ 42 secretion, responding to βand γ-secretase inhibitors that reduced the Aβ 42 consequential tau phosphorylation too. 119,120 Also, the few studies conducted on iPSCs from sAD patients presented increased Aβ levels with an altered Aβ 42/40 ratio and an increased APP expression, 121 but the results were somehow inhomogeneous, reflecting the complexity of the pathogenesis of sAD. 120 Despite iPSCs are the newest form of stem cell therapies, neurons derived from iPSCs are not devoid of limitations.…”

Section: Stem Cell Therapies and Personalized Medicine In Admentioning

confidence: 99%

“…119,120 Also, the few studies conducted on iPSCs from sAD patients presented increased Aβ levels with an altered Aβ 42/40 ratio and an increased APP expression, 121 but the results were somehow inhomogeneous, reflecting the complexity of the pathogenesis of sAD. 120 Despite iPSCs are the newest form of stem cell therapies, neurons derived from iPSCs are not devoid of limitations. Indeed, their high proliferative capacity may cause the risk of tumor formation.…”

Section: Stem Cell Therapies and Personalized Medicine In Admentioning

confidence: 99%

“…122 Thanks to a miniaturized spinning bioreactor, other groups generated forebrain-specific organoids from human iPSCs that recapitulate key features of human cortical development. 120 These systems can be used to evaluate the development of a pathological state and eventually to test therapeutics. Because of its embryonic/ fetal nature, some criticisms have been raised about the unsuitableness of this model to recapitulate events occurring in the late phases of the disease.…”

Section: Stem Cell Therapies and Personalized Medicine In Admentioning

confidence: 99%

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<p>Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer’s Disease: A State-of-the-Art (2017–2020)</p>

Binda¹,

Murano²,

Rivolta³

2020

IJN

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The field of nanomedicine is constantly expanding. Since the first work dated in 1999, almost 28 thousand articles have been published, and more and more are published every year: just think that only in the last five years 20,855 have come out (source PUBMED) including original research and reviews. The goal of this review is to present the current knowledge about nanomedicine in Alzheimer's disease, a widespread neurodegenerative disorder in the over 60 population that deeply affects memory and cognition. Thus, after a brief introduction on the pathology and on the state-of-the-art research for NPs passing the BBB, special attention is placed to new targets that can enter the interest of nanoparticle designers and to new promising therapies. The authors performed a literature review limited to the last three years (2017-2020) of available studies with the intention to present only novel formulations or approaches where at least in vitro studies have been performed. This choice was made because, while limiting the sector to nanotechnology applied to Alzheimer, an organic census of all the relevant news is difficult to obtain.

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“…Brain organoids derived from pluripotent stem cells can effectively model human cortical development and recapitulate its 3D cytoarchitecture; thus, opening a new window of opportunities to further investigate disease pathogenesis in vitro [40,41]. Moreover, the 3D brain organoids can reveal particular disease phenotypes, which are barely observed in 2D culture systems [42]. For the first time was the concept of whole-brain organoid formation within the same 3D platform published by Lancaster and Knoblich [43].…”

Section: Ipsc-derived Brain Organoid Modelsmentioning

confidence: 99%

Recent Overview of the Use of iPSCs Huntington’s Disease Modeling and Therapy

Csöbönyeiová

Polák

Danišovič

2020

IJMS

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Huntington’s disease (HD) is an inherited, autosomal dominant, degenerative disease characterized by involuntary movements, cognitive decline, and behavioral impairment ending in death. HD is caused by an expansion in the number of CAG repeats in the huntingtin gene on chromosome 4. To date, no effective therapy for preventing the onset or progression of the disease has been found, and many symptoms do not respond to pharmacologic treatment. However, recent results of pre-clinical trials suggest a beneficial effect of stem-cell-based therapy. Induced pluripotent stem cells (iPSCs) represent an unlimited cell source and are the most suitable among the various types of autologous stem cells due to their patient specificity and ability to differentiate into a variety of cell types both in vitro and in vivo. Furthermore, the cultivation of iPSC-derived neural cells offers the possibility of studying the etiopathology of neurodegenerative diseases, such as HD. Moreover, differentiated neural cells can organize into three-dimensional (3D) organoids, mimicking the complex architecture of the brain. In this article, we present a comprehensive review of recent HD models, the methods for differentiating HD–iPSCs into the desired neural cell types, and the progress in gene editing techniques leading toward stem-cell-based therapy.

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Using induced pluripotent stem cell neuronal models to study neurodegenerative diseases

Cited by 28 publications

References 167 publications

G₄C₂repeat RNA mediates the disassembly of the nuclear pore complex in C9orf72 ALS/FTD

G₄C₂repeat RNA mediates the disassembly of the nuclear pore complex in C9orf72 ALS/FTD

<p>Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer’s Disease: A State-of-the-Art (2017–2020)</p>

Recent Overview of the Use of iPSCs Huntington’s Disease Modeling and Therapy

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Using induced pluripotent stem cell neuronal models to study neurodegenerative diseases

Cited by 28 publications

References 167 publications

G4C2repeat RNA mediates the disassembly of the nuclear pore complex in C9orf72 ALS/FTD

G4C2repeat RNA mediates the disassembly of the nuclear pore complex in C9orf72 ALS/FTD

<p>Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer’s Disease: A State-of-the-Art (2017–2020)</p>

Recent Overview of the Use of iPSCs Huntington’s Disease Modeling and Therapy

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G₄C₂repeat RNA mediates the disassembly of the nuclear pore complex in C9orf72 ALS/FTD

G₄C₂repeat RNA mediates the disassembly of the nuclear pore complex in C9orf72 ALS/FTD