Extracellular Pgk1 enhances neurite outgrowth of motoneurons through Nogo66/NgR-independent targeting of NogoA

Lin, Cheng Yung; Wu, Chia Lun; Lee, Kok Zhi; Chen, You Jei; Zhang, Po Hsiang; Chang, Chia Yu; Harn, Horng Jyh; Lin, Shinn Zong; Tsai, Huai Jen

doi:10.7554/elife.49175

Cited by 19 publications

(25 citation statements)

References 48 publications

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“…Total protein was extracted from embryos and analyzed on 10% SDS-PAGE followed by western blot analysis according to the procedures described by Lin et al [ 16 ], except that the yolk was removed by deyolking buffer (55 mM NaCl, 1.8 mM KCl and 1.25 mM NaHCO 3 ) and antibodies against Flag (Abcam, Cambridge, UK; 1:5000 dilution), α-tubulin (Sigma-Aldrich, St. Louis, MO, USA; 1:5000 dilution), mouse-HRP (Santa Cruz, Santa Cruz, CA, USA; 1:5000 dilution), and rabbit-HRP (Santa Cruz; 1:5000 dilution) were used.…”

Section: Methodsmentioning

confidence: 99%

Effect of Mutated ids Overexpression on IDS Enzyme Activity and Developmental Phenotypes in Zebrafish Embryos: A Valuable Index for Assessing Critical Point-Mutations Associated with Mucopolysaccharidosis Type II Occurrence in Humans

Lin

Chen

et al. 2020

Diagnostics

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Mucopolysaccharidosis type II (MPS II) is an X-linked disorder resulting from a deficiency in iduronate 2-sulfatase (IDS), which is reported to be caused by gene mutations in the iduronate 2-sulfatase (IDS) gene. Many IDS mutation sites have not yet had their causal relationship with MPS II characterized. We employed a gain-of-function strategy whereby we microinjected different mutated zebrafish ids (z-ids) mRNAs corresponded to human IDS gene into zebrafish embryos, and then measured their total IDS enzymatic activity and observed the occurrence of defective phenotypes during embryonic development. We examined three known mutation sites for human IDS genes (h-IDS) associated with MPS II symptoms, including h-IDS-P86L, -S333L and -R468W, which corresponded to z-ids-P80L, -S327L and -R454W. When these three mutated z-ids mRNAs were overexpressed in zebrafish embryos, the IDS enzymatic activity of the total proteins extracted from the injected embryos was not increased compared with the endogenous IDS of the untreated embryos, which suggests that the IDS enzymatic activity of these three mutated z-ids was totally lost, as expected. Additionally, we observed defective phenotypes in these injected embryos, resulting from the failed IDS enzyme breakdown, which, in turn, has a dominant negative effect on the endogenous wild-type IDS function. These phenotypes were similar to the clinical symptoms observed in MPS II pathogenesis. We further studied six uncharacterized IDS mutation sites as identified by the Taiwanese MPS newborn screening programs. We propose a novel IDS enzyme activity assay combined with phenotypic observation in zebrafish embryos, as an alternative platform for quickly providing a valuable index for preliminarily assessment of any identified IDS point mutation gene that has not yet been characterized, in the context of its role in MPS II development.

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Section: Methodsmentioning

confidence: 99%

Effect of Mutated ids Overexpression on IDS Enzyme Activity and Developmental Phenotypes in Zebrafish Embryos: A Valuable Index for Assessing Critical Point-Mutations Associated with Mucopolysaccharidosis Type II Occurrence in Humans

Lin

Chen

et al. 2020

Diagnostics

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“…Studies have unveiled additional abnormalities that may be related to the onset of sporadic and non-SOD1 familial ALS [ 56 ]. These include the impairment of neuronal cytoskeletal function, protein instability, aggregation and degradation of RNA/DNA-binding proteins, and the detrimental roles of non-neuronal cells (such as astrocytes) that can be toxic and degenerative to motor neurons [ 111 ]. Several factors cause difficulty in finding effective therapies for ALS.…”

Section: Neurodegenerative Diseases and Stem Cell Therapy Strategimentioning

confidence: 99%

Regenerative Stem Cell Therapy for Neurodegenerative Diseases: An Overview

Sivandzade

Cucullo

2021

IJMS

128

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Neurodegenerative diseases resulting from the progressive loss of structure and/or function of neurons contribute to different paralysis degrees and loss of cognition and sensation. The lack of successful curative therapies for neurodegenerative disorders leads to a considerable burden on society and a high economic impact. Over the past 20 years, regenerative cell therapy, also known as stem cell therapy, has provided an excellent opportunity to investigate potentially powerful innovative strategies for treating neurodegenerative diseases. This is due to stem cells’ capability to repair injured neuronal tissue by replacing the damaged or lost cells with differentiated cells, providing a conducive environment that is in favor of regeneration, or protecting the existing healthy neurons and glial cells from further damage. Thus, in this review, the various types of stem cells, the current knowledge of stem-cell-based therapies in neurodegenerative diseases, and the recent advances in this field are summarized. Indeed, a better understanding and further studies of stem cell technologies cause progress into realistic and efficacious treatments of neurodegenerative disorders.

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“…Neuromuscular junction (NMJ) degeneration is the early cytopathy of ALS that directly influences motor function. Reports also suggested that cytopathic cells, motor neurons, and skeletal muscles in the NMJ influenced each other to promote the progression of ALS [96,97]. Thus, NMJ models represent in vitro tools for clarifying the early progression of ALS.…”

Section: Ipscs For Screening Of Therapeutic Compounds For Alsmentioning

confidence: 99%

Induced Pluripotent Stem Cell (iPSC)-Based Neurodegenerative Disease Models for Phenotype Recapitulation and Drug Screening

et al. 2020

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Neurodegenerative diseases represent a significant unmet medical need in our aging society. There are no effective treatments for most of these diseases, and we know comparatively little regarding pathogenic mechanisms. Among the challenges faced by those involved in developing therapeutic drugs for neurodegenerative diseases, the syndromes are often complex, and small animal models do not fully recapitulate the unique features of the human nervous system. Human induced pluripotent stem cells (iPSCs) are a novel technology that ideally would permit us to generate neuronal cells from individual patients, thereby eliminating the problem of species-specificity inherent when using animal models. Specific phenotypes of iPSC-derived cells may permit researchers to identify sub-types and to distinguish among unique clusters and groups. Recently, iPSCs were used for drug screening and testing for neurologic disorders including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), spinocerebellar atrophy (SCA), and Zika virus infection. However, there remain many challenges still ahead, including how one might effectively recapitulate sporadic disease phenotypes and the selection of ideal phenotypes and for large-scale drug screening. Fortunately, quite a few novel strategies have been developed that might be combined with an iPSC-based model to solve these challenges, including organoid technology, single-cell RNA sequencing, genome editing, and deep learning artificial intelligence. Here, we will review current applications and potential future directions for iPSC-based neurodegenerative disease models for critical drug screening.

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Extracellular Pgk1 enhances neurite outgrowth of motoneurons through Nogo66/NgR-independent targeting of NogoA

Cited by 19 publications

References 48 publications

Effect of Mutated ids Overexpression on IDS Enzyme Activity and Developmental Phenotypes in Zebrafish Embryos: A Valuable Index for Assessing Critical Point-Mutations Associated with Mucopolysaccharidosis Type II Occurrence in Humans

Effect of Mutated ids Overexpression on IDS Enzyme Activity and Developmental Phenotypes in Zebrafish Embryos: A Valuable Index for Assessing Critical Point-Mutations Associated with Mucopolysaccharidosis Type II Occurrence in Humans

Regenerative Stem Cell Therapy for Neurodegenerative Diseases: An Overview

Induced Pluripotent Stem Cell (iPSC)-Based Neurodegenerative Disease Models for Phenotype Recapitulation and Drug Screening

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