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Article: Rising Stars: Astrocytes as a Therapeutic Target for ALS Disease.

Izrael, Michal / Slutsky, Shalom Guy / Revel, Michel

2020 Volume 14, Page(s) 824

Abstract: Amyotrophic lateral sclerosis (ALS) is a multifactorial disease, characterized by a progressive loss of motor neurons that eventually leads to paralysis and death. The current ALS-approved drugs modestly change the clinical course of the disease. The ... ...

Abstract	Amyotrophic lateral sclerosis (ALS) is a multifactorial disease, characterized by a progressive loss of motor neurons that eventually leads to paralysis and death. The current ALS-approved drugs modestly change the clinical course of the disease. The mechanism by which motor neurons progressively degenerate remains unclear but entails a non-cell autonomous process. Astrocytes impaired biological functionality were implicated in multiple neurodegenerative diseases, including ALS, frontotemporal dementia (FTD), Parkinson's disease (PD), and Alzheimer disease (AD). In ALS disease patients, A1 reactive astrocytes were found to play a key role in the pathology of ALS disease and death of motor neurons, via loss or gain of function or acquired toxicity. The contribution of astrocytes to the maintenance of motor neurons by diverse mechanisms makes them a promising therapeutic candidate for the treatment of ALS. Therapeutic approaches targeting at modulating the function of endogenous astrocytes or replacing lost functionality by transplantation of healthy astrocytes, may contribute to the development of therapies which might slow down or even halt the progression ALS diseases. The proposed mechanisms by which astrocytes can potentially ameliorate ALS progression and the status of ALS clinical studies involving astrocytes are discussed.
Language	English
Publishing date	2020-07-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2020.00824
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Article: Astrocytes Downregulate Inflammation in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome: Applicability to COVID-19.

Izrael, Michal / Molakandov, Kfir / Revel, Ariel / Slutsky, Shalom Guy / Sonnenfeld, Tehila / Weiss, Julia Miriam / Revel, Michel

Frontiers in medicine

2021 Volume 8, Page(s) 740071

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2021-10-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2021.740071
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Article ; Online: Safety and efficacy of first-in-man intrathecal injection of human astrocytes (AstroRx®) in ALS patients: phase I/IIa clinical trial results.

Gotkine, Marc / Caraco, Yoseph / Lerner, Yossef / Blotnick, Simcha / Wanounou, Maor / Slutsky, Shalom Guy / Chebath, Judith / Kuperstein, Graciela / Estrin, Elena / Ben-Hur, Tamir / Hasson, Arik / Molakandov, Kfir / Sonnenfeld, Tehila / Stark, Yafit / Revel, Ariel / Revel, Michel / Izrael, Michal

Journal of translational medicine

2023 Volume 21, Issue 1, Page(s) 122

Abstract: Background: Malfunction of astrocytes is implicated as one of the pathological factors of ALS. Thus, intrathecal injection of healthy astrocytes in ALS can potentially compensate for the diseased astrocytes. AstroRx® is an allogeneic cell-based product, ...

Abstract	Background: Malfunction of astrocytes is implicated as one of the pathological factors of ALS. Thus, intrathecal injection of healthy astrocytes in ALS can potentially compensate for the diseased astrocytes. AstroRx® is an allogeneic cell-based product, composed of healthy and functional human astrocytes derived from embryonic stem cells. AstroRx® was shown to clear excessive glutamate, reduce oxidative stress, secrete various neuroprotective factors, and act as an immunomodulator. Intrathecal injection of AstroRx® to animal models of ALS slowed disease progression and extended survival. Here we report the result of a first-in-human clinical study evaluating intrathecal injection of AstroRx® in ALS patients. Methods: We conducted a phase I/IIa, open-label, dose-escalating clinical trial to evaluate the safety, tolerability, and therapeutic effects of intrathecal injection of AstroRx® in patients with ALS. Five patients were injected intrathecally with a single dose of 100 × 10 Results: A single administration of AstroRx® at either low or high doses was safe and well tolerated. No adverse events (AEs) related to AstroRx® itself were reported. Transient AEs related to the Intrathecal (IT) procedure were all mild to moderate. The study demonstrated a clinically meaningful effect that was maintained over the first 3 months after treatment, as measured by the pre-post slope change in ALSFRS-R. In the 100 × 10 Conclusions: Overall, these findings suggest that a single IT administration of AstroRx® to ALS patients at a dose of 100 × 10 Trial registration: NCT03482050.
MeSH term(s)	Humans ; Amyotrophic Lateral Sclerosis/therapy ; Astrocytes ; Injections, Spinal ; Mesenchymal Stem Cell Transplantation/methods
Language	English
Publishing date	2023-02-14
Publishing country	England
Document type	Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-023-03903-3
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Article ; Online: Astrocytes Downregulate Inflammation in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome

Michal Izrael / Kfir Molakandov / Ariel Revel / Shalom Guy Slutsky / Tehila Sonnenfeld / Julia Miriam Weiss / Michel Revel

Frontiers in Medicine, Vol

Applicability to COVID-19

2021 Volume 8

Abstract: Background: An acute respiratory distress syndrome (ARDS) is caused by the increased amounts of pro-inflammatory cytokines and neutrophil-mediated tissue injury. To date, there is no effective treatment for the ARDS available, while the need for one is ... ...

Abstract	Background: An acute respiratory distress syndrome (ARDS) is caused by the increased amounts of pro-inflammatory cytokines and neutrophil-mediated tissue injury. To date, there is no effective treatment for the ARDS available, while the need for one is growing due to the most severe complications of the current coronavirus disease-2019 (COVID-19) pandemic. The human astrocytes (AstroRx) have shown immunomodulatory properties in the central nervous system (CNS). This study aimed to evaluate the capacity of astrocytes to decrease lung inflammation and to be applied as a treatment therapy in ARDS.Methods: First, we assessed the ability of clinical-grade AstroRx to suppress T-cell proliferation in a mixed lymphocyte reaction test. Next, we tested the therapeutical potential of AstroRx cells in a lipopolysaccharide (LPS)-based ARDS mouse model by injecting AstroRx intravenously (i.v). We determined the degree of lung injury by using a severity scoring scale of 0–2, based on the American Thoracic Society. The scoring measured the presence of neutrophils, fibrin deposits, and the thickening of alveolar walls. The state of inflammation was further assessed by quantifying the immune-cell infiltration to the bronchoalveolar lavage fluid (BALF) and by the presence of proinflammatory cytokines and chemokines in the BALF and serum.Results: We detected that AstroRx cells were capable to suppress T-cell proliferation in vitro after exposure to the mitogen concanavalin A (ConA). In vivo, AstroRx cells were able to lower the degree of lung injury in LPS-treated animals compared with the sham injected animals (P = 0.039). In this study, 30% of AstroRx treated mice showed no lung lesions (responder mice), these mice presented a steady number of eosinophils, T cells, and neutrophils comparable with the level of naïve control mice. The inflammatory cytokines and chemokines, such as TNFα, IL1b, IL-6, and CXCL1, were also kept in check in responder AstroRx-treated mice and were not upregulated as in the sham-injected mice (P < ...
Keywords	ARDS ; astrocytes ; immune-modulation ; inflammation ; embryonic stem cells ; Medicine (General) ; R5-920
Subject code	630
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: Compact MRI for the detection of teratoma development following intrathecal human embryonic stem cell injection in NOD-SCID mice.

Ramot, Yuval / Schiffenbauer, Yael S / Amouyal, Netanel / Ezov, Nathan / Steiner, Michal / Izrael, Michal / Lavon, Neta / Hasson, Arik / Revel, Michel / Nyska, Abraham

Neurotoxicology

2017 Volume 59, Page(s) 27–32

Abstract: Stem cells are emerging as a promising new treatment modality for a variety of central nervous system disorders. However, their use is hampered by the potential for the development of teratomas and other tumors. Therefore, there is a crucial need for the ...

Abstract	Stem cells are emerging as a promising new treatment modality for a variety of central nervous system disorders. However, their use is hampered by the potential for the development of teratomas and other tumors. Therefore, there is a crucial need for the development of methods for detecting teratomas in preclinical safety studies. The aim of the current study is to assess the ability of a compact Magnetic Resonance Imaging (MRI) system to detect teratoma formation in mice. Five NOD-SCID mice were injected intrathecally with human embryonic stem cells (hESCs), with two mice serving as controls. In vivo MRI was performed on days 25 and 48, and ex vivo MRI was performed after scheduled euthanization (day 55). MRI results were compared to histopathology findings. Two animals injected with hESCs developed hind-limb paresis and paralysis, necessitating premature euthanization. MRI examination revealed abnormal pale areas in the spinal cord and brain, which correlated histopathologically with teratomas. This preliminary study shows the efficacy of compact MRI systems in the detection of small teratomas following intrathecal injection of hESCs in a highly sensitive manner. Although these results should be validated in larger studies, they provide further evidence that the use of MRI in longitudinal studies offers a new monitoring strategy for preclinical testing of stem cell applications.
Language	English
Publishing date	2017-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	800820-6
ISSN	1872-9711 ; 0161-813X
ISSN (online)	1872-9711
ISSN	0161-813X
DOI	10.1016/j.neuro.2017.01.003
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Article ; Online: Human iPSC-derived astrocytes from ALS patients with mutated C9ORF72 show increased oxidative stress and neurotoxicity.

Birger, Anastasya / Ben-Dor, Israel / Ottolenghi, Miri / Turetsky, Tikva / Gil, Yaniv / Sweetat, Sahar / Perez, Liat / Belzer, Vitali / Casden, Natania / Steiner, Debora / Izrael, Michal / Galun, Eithan / Feldman, Eva / Behar, Oded / Reubinoff, Benjamin

EBioMedicine

2019 Volume 50, Page(s) 274–289

Abstract: Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons (MNs). It was shown that human astrocytes with mutations in genes associated with ALS, like C9orf72 (C9) or SOD1, reduce survival of ... ...

Abstract	Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons (MNs). It was shown that human astrocytes with mutations in genes associated with ALS, like C9orf72 (C9) or SOD1, reduce survival of MNs. Astrocyte toxicity may be related to their dysfunction or the release of neurotoxic factors. Methods: We used human induced pluripotent stem cell-derived astrocytes from ALS patients carrying C9orf72 mutations and non-affected donors. We utilized these cells to investigate astrocytic induced neuronal toxicity, changes in astrocyte transcription profile as well as changes in secretome profiles. Findings: We report that C9-mutated astrocytes are toxic to MNs via soluble factors. The toxic effects of astrocytes are positively correlated with the length of astrocyte propagation in culture, consistent with the age-related nature of ALS. We show that C9-mutated astrocytes downregulate the secretion of several antioxidant proteins. In line with these findings, we show increased astrocytic oxidative stress and senescence. Importantly, media conditioned by C9-astrocytes increased oxidative stress in wild type MNs. Interpretation: Our results suggest that dysfunction of C9-astrocytes leads to oxidative stress of themselves and MNs, which probably contributes to neurodegeneration. Our findings suggest that therapeutic strategies in familial ALS must not only target MNs but also focus on astrocytes to abrogate nervous system injury.
MeSH term(s)	Amyotrophic Lateral Sclerosis/etiology ; Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/physiopathology ; Animals ; Astrocytes/cytology ; Astrocytes/metabolism ; Biomarkers ; C9orf72 Protein/genetics ; Cells, Cultured ; Cellular Reprogramming ; Cellular Senescence/genetics ; Cerebral Cortex/cytology ; Cerebral Cortex/metabolism ; Disease Models, Animal ; Gene Expression Profiling ; Glutamic Acid/metabolism ; Humans ; Induced Pluripotent Stem Cells/cytology ; Mice ; Motor Neurons/metabolism ; Mutation ; Oxidative Stress ; Proteomics/methods ; Reactive Oxygen Species/metabolism
Chemical Substances	Biomarkers ; C9orf72 Protein ; Reactive Oxygen Species ; Glutamic Acid (3KX376GY7L)
Language	English
Publishing date	2019-11-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2019.11.026
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Article ; Online: Human iPSC-derived astrocytes from ALS patients with mutated C9ORF72 show increased oxidative stress and neurotoxicity

Anastasya Birger / Israel Ben-Dor / Miri Ottolenghi / Tikva Turetsky / Yaniv Gil / Sahar Sweetat / Liat Perez / Vitali Belzer / Natania Casden / Debora Steiner / Michal Izrael / Eithan Galun / Eva Feldman / Oded Behar / Benjamin Reubinoff

EBioMedicine, Vol 50, Iss , Pp 274-

2019 Volume 289

Abstract	Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons (MNs). It was shown that human astrocytes with mutations in genes associated with ALS, like C9orf72 (C9) or SOD1, reduce survival of MNs. Astrocyte toxicity may be related to their dysfunction or the release of neurotoxic factors. Methods: We used human induced pluripotent stem cell-derived astrocytes from ALS patients carrying C9orf72 mutations and non-affected donors. We utilized these cells to investigate astrocytic induced neuronal toxicity, changes in astrocyte transcription profile as well as changes in secretome profiles. Findings: We report that C9-mutated astrocytes are toxic to MNs via soluble factors. The toxic effects of astrocytes are positively correlated with the length of astrocyte propagation in culture, consistent with the age-related nature of ALS. We show that C9-mutated astrocytes downregulate the secretion of several antioxidant proteins. In line with these findings, we show increased astrocytic oxidative stress and senescence. Importantly, media conditioned by C9-astrocytes increased oxidative stress in wild type MNs. Interpretation: Our results suggest that dysfunction of C9-astrocytes leads to oxidative stress of themselves and MNs, which probably contributes to neurodegeneration. Our findings suggest that therapeutic strategies in familial ALS must not only target MNs but also focus on astrocytes to abrogate nervous system injury. Keywords: Amyotrophic lateral sclerosis, iPSC, Astrocytes, Oxidative stress, Neurotoxicity, Senescence
Keywords	Medicine ; R ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2019-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Survival, differentiation, and reversal of heroin neurobehavioral teratogenicity in mice by transplanted neural stem cells derived from embryonic stem cells.

Kazma, Meital / Izrael, Michal / Revel, Michel / Chebath, Judith / Yanai, Joseph

Journal of neuroscience research

2010 Volume 88, Issue 2, Page(s) 315–323

Abstract: Cell therapies in animal models of neurobehavioral defects are normally derived from neural stem cells (NSC) of the developing cortex. However, the clinical feasibility of NSC therapies would be greatly improved by deriving transplanted cells and from a ... ...

Abstract	Cell therapies in animal models of neurobehavioral defects are normally derived from neural stem cells (NSC) of the developing cortex. However, the clinical feasibility of NSC therapies would be greatly improved by deriving transplanted cells and from a tissue culture source that is self-renewing, containing cells that potentially differentiate into the desired neuronal phenotypes. These cultures can be engineered to contain the appropriate factors to support their therapeutic action and likely evoke lesser immune reactions. In the current study, we employed our model of mice neurobehaviorally impaired via prenatal exposure to heroin, to test the therapeutic efficacy of NSC derived from murine embryonic stem cells culture (ESC). The culture contained elongated bipolar cells, 90% of which are positive for nestin, the intermediate filament protein found in neural precursors. After removal of growth factors, the NSC differentiated into neurons (34.0% +/- 3.8% NF-160 positive), including cholinergic cells (ChAT positive), oligodendrocytes (29.9% +/- 4.2% O(4)), and astrocytes (36.1% +/- 4.7% GFAP positive). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis confirmed the immunocytochemical findings. Mice made deficient in Morris maze behavior by prenatal heroin exposure (10 mg/kg heroin s.c. on gestational days 9-18) were transplanted into the hippocampus region on postnatal day 35 with the ES culture-derived NSC (ES-NSC) labeled with dialkylcarbocyanine (Dil) cell tracker. Dil+ and NF160+ cells were detected in the hippocampal region (50% +/- 8% survival). The transplantation completely restored maze performance to normal; e.g., on day 3, transplantation improved the behavior from the deficient level of 11.9-sec latency to the control of 5.6-sec latency (44.5% improvement).
MeSH term(s)	Animals ; Cell Differentiation/physiology ; Cell Survival/physiology ; Cognition Disorders/chemically induced ; Cognition Disorders/physiopathology ; Cognition Disorders/surgery ; Disease Models, Animal ; Embryonic Stem Cells/physiology ; Female ; Heroin/toxicity ; Male ; Maze Learning/physiology ; Mice ; Narcotics/toxicity ; Neurogenesis/physiology ; Neurons/physiology ; Neurons/transplantation ; Opioid-Related Disorders/physiopathology ; Opioid-Related Disorders/surgery ; Pregnancy ; Prenatal Exposure Delayed Effects/surgery ; Stem Cell Transplantation ; Stem Cells/physiology
Chemical Substances	Narcotics ; Heroin (70D95007SX)
Language	English
Publishing date	2010-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	195324-2
ISSN	1097-4547 ; 0360-4012
ISSN (online)	1097-4547
ISSN	0360-4012
DOI	10.1002/jnr.22193
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Zs.A 1232: Show issues

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Article ; Online: Safety and efficacy of human embryonic stem cell-derived astrocytes following intrathecal transplantation in SOD1

Izrael, Michal / Slutsky, Shalom Guy / Admoni, Tamar / Cohen, Louisa / Granit, Avital / Hasson, Arik / Itskovitz-Eldor, Joseph / Krush Paker, Lena / Kuperstein, Graciela / Lavon, Neta / Yehezkel Ionescu, Shiran / Solmesky, Leonardo Javier / Zaguri, Rachel / Zhuravlev, Alina / Volman, Ella / Chebath, Judith / Revel, Michel

Stem cell research & therapy

2018 Volume 9, Issue 1, Page(s) 152

Abstract: Background: Amyotrophic lateral sclerosis (ALS) is a motor neuron (MN) disease characterized by the loss of MNs in the central nervous system. As MNs die, patients progressively lose their ability to control voluntary movements, become paralyzed and ... ...

Abstract	Background: Amyotrophic lateral sclerosis (ALS) is a motor neuron (MN) disease characterized by the loss of MNs in the central nervous system. As MNs die, patients progressively lose their ability to control voluntary movements, become paralyzed and eventually die from respiratory/deglutition failure. Despite the selective MN death in ALS, there is growing evidence that malfunctional astrocytes play a crucial role in disease progression. Thus, transplantation of healthy astrocytes may compensate for the diseased astrocytes. Methods: We developed a good manufacturing practice-grade protocol for generation of astrocytes from human embryonic stem cells (hESCs). The first stage of our protocol is derivation of astrocyte progenitor cells (APCs) from hESCs. These APCs can be expanded in large quantities and stored frozen as cell banks. Further differentiation of the APCs yields an enriched population of astrocytes with more than 90% GFAP expression (hES-AS). hES-AS were injected intrathecally into hSOD1 Results: In vitro, hES-AS possess the activities of functional healthy astrocytes, including glutamate uptake, promotion of axon outgrowth and protection of MNs from oxidative stress. A secretome analysis shows that these hES-AS also secrete several inhibitors of metalloproteases as well as a variety of neuroprotective factors (e.g. TIMP-1, TIMP-2, OPN, MIF and Midkine). Intrathecal injections of the hES-AS into transgenic hSOD1 Conclusion: Our findings demonstrate the safety and potential therapeutic benefits of intrathecal injection of hES-AS for the treatment of ALS.
MeSH term(s)	Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/pathology ; Animals ; Astrocytes/metabolism ; Disease Models, Animal ; Human Embryonic Stem Cells/metabolism ; Humans ; Injections, Spinal/methods ; Mice ; Rats ; Superoxide Dismutase-1/genetics ; Superoxide Dismutase-1/metabolism
Chemical Substances	Superoxide Dismutase-1 (EC 1.15.1.1)
Language	English
Publishing date	2018-06-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-018-0890-5
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Article ; Online: Induction of oligodendrocyte differentiation and in vitro myelination by inhibition of rho-associated kinase.

Pedraza, Carlos E / Taylor, Christopher / Pereira, Albertina / Seng, Michelle / Tham, Chui-Se / Izrael, Michal / Webb, Michael

ASN neuro

2014 Volume 6, Issue 4

Abstract: In inflammatory demyelinating diseases such as multiple sclerosis (MS), myelin degradation results in loss of axonal function and eventual axonal degeneration. Differentiation of resident oligodendrocyte precursor cells (OPCs) leading to remyelination of ...

Abstract	In inflammatory demyelinating diseases such as multiple sclerosis (MS), myelin degradation results in loss of axonal function and eventual axonal degeneration. Differentiation of resident oligodendrocyte precursor cells (OPCs) leading to remyelination of denuded axons occurs regularly in early stages of MS but halts as the pathology transitions into progressive MS. Pharmacological potentiation of endogenous OPC maturation and remyelination is now recognized as a promising therapeutic approach for MS. In this study, we analyzed the effects of modulating the Rho-A/Rho-associated kinase (ROCK) signaling pathway, by the use of selective inhibitors of ROCK, on the transformation of OPCs into mature, myelinating oligodendrocytes. Here we demonstrate, with the use of cellular cultures from rodent and human origin, that ROCK inhibition in OPCs results in a significant generation of branches and cell processes in early differentiation stages, followed by accelerated production of myelin protein as an indication of advanced maturation. Furthermore, inhibition of ROCK enhanced myelin formation in cocultures of human OPCs and neurons and remyelination in rat cerebellar tissue explants previously demyelinated with lysolecithin. Our findings indicate that by direct inhibition of this signaling molecule, the OPC differentiation program is activated resulting in morphological and functional cell maturation, myelin formation, and regeneration. Altogether, we show evidence of modulation of the Rho-A/ROCK signaling pathway as a viable target for the induction of remyelination in demyelinating pathologies.
MeSH term(s)	Animals ; Animals, Newborn ; Brain/cytology ; Cell Differentiation/drug effects ; Cell Differentiation/physiology ; Cells, Cultured ; Coculture Techniques ; Embryo, Mammalian ; Enzyme Inhibitors/pharmacology ; Ganglia, Spinal/cytology ; Humans ; In Vitro Techniques ; Mice ; Mice, Inbred C57BL ; Myelin Proteins/metabolism ; Myelin Sheath/metabolism ; Nerve Growth Factor/pharmacology ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neuroglia/physiology ; Oligodendroglia ; Optic Nerve/cytology ; Rats ; Stem Cells ; Time Factors ; rho-Associated Kinases/metabolism
Chemical Substances	Enzyme Inhibitors ; Myelin Proteins ; Nerve Tissue Proteins ; Nerve Growth Factor (9061-61-4) ; rho-Associated Kinases (EC 2.7.11.1)
Language	English
Publishing date	2014-06-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2485467-0
ISSN	1759-0914 ; 1759-0914
ISSN (online)	1759-0914
ISSN	1759-0914
DOI	10.1177/1759091414538134
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