<i>n</i>‐butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in <scp>SOD</scp>1<sup>G93A</sup> mouse model of amyotrophic lateral sclerosis

Zhou, Qin; Zhang, Jing Jing; Li, Song; Chen, Sheng

doi:10.1111/cns.12681

Cited by 37 publications

(27 citation statements)

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“…As for the life span, the time of animals death was defined as the day when mice could no longer right themselves when they were placed on their back for 30 seconds . Mice were then sacrificed to reduce further pain from respiratory failure according to animal care guidelines.…”

Section: Methodsmentioning

confidence: 99%

“…For MNs counting, 1 of every 4 slices and a total of fifty slices were selected for Nissl staining. The MNs in the anterior horns of both sides were counted by an independent investigator who was blinded to genotype and group according to the criterion as described in our previous study . We also counted the number of MNs by immunofluorescent staining with SMI‐32 antibody.…”

Section: Methodsmentioning

confidence: 99%

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Repurposing carbamazepine for the treatment of amyotrophic lateral sclerosis in SOD1‐G93A mouse model

et al. 2018

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Repurposing carbamazepine for the treatment of amyotrophic lateral sclerosis in SOD1‐G93A mouse model

et al. 2018

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“…NBP has been demonstrated to exert neuroprotective roles in cerebral ischemia and vascular dementia ( 135 , 136 ). In preclinical work, NBP reduced glial cell activation, attenuated MN death, and thus prolonged the survival interval of SOD1 G93A mice ( 137 – 139 ), suggesting this compound might be a novel treatment for ALS. A phase II and III multicenter, randomized, double-blind, placebo-controlled clinical trial with oral administration of NBP in ALS patients is ongoing in China to evaluate its efficacy and safety ( Identifier: ChiCTR-IPR-15007365).…”

Section: Pharmacological Strategies Targeting Neuroinflammation In Almentioning

confidence: 98%

Role of Neuroinflammation in Amyotrophic Lateral Sclerosis: Cellular Mechanisms and Therapeutic Implications

2017

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects upper motor neurons (MNs) comprising the corticospinal tract and lower MNs arising from the brain stem nuclei and ventral roots of the spinal cord, leading to fatal paralysis. Currently, there are no effective therapies for ALS. Increasing evidence indicates that neuroinflammation plays an important role in ALS pathogenesis. The neuroinflammation in ALS is characterized by infiltration of lymphocytes and macrophages, activation of microglia and reactive astrocytes, as well as the involvement of complement. In this review, we focus on the key cellular players of neuroinflammation during the pathogenesis of ALS by discussing not only their detrimental roles but also their immunomodulatory actions. We will summarize the pharmacological therapies for ALS that target neuroinflammation, as well as recent advances in the field of stem cell therapy aimed at modulating the inflammatory environment to preserve the remaining MNs in ALS patients and animal models of the disease.

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“…In recent years, many molecules able to modulate the autophagy process have been tested in order to prevent mSOD1-induced motor neuron death [8,45,50].…”

Section: Discussionmentioning

confidence: 99%

PACAP Modulates the Autophagy Process in an In Vitro Model of Amyotrophic Lateral Sclerosis

D’Amico¹,

Maugeri

Saccone

et al. 2020

IJMS

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of complex etiology leading to motor neuron degeneration. Many gene alterations cause this pathology, including mutation in Cu, Zn superoxide dismutase (SOD1), which leads to its gain of function. Mutant SOD1 proteins are prone to aberrant misfolding and create aggregates that impair autophagy. The hypoxic stress is strictly linked to the disease progression since it induces uncontrolled autophagy activation and the consequent high rates of cell death. Previously, we showed that pituitary adenylate cyclase-activating polypeptide (PACAP) exerts neurotrophic activity in cultured mSOD1 motor neurons exposed to serum deprivation. To date, no studies have examined whether the protective effect of PACAP on mSOD1 cells exposed to hypoxic insult is mediated through the regulation of the autophagy process. In the present study, we used the neuroblastoma-spinal cord-34 (NSC-34) cell line, stably expressing human wild type or mutant SOD1 G93A, to represent a well characterized in vitro model of a familial form of ALS. These cells were exposed to 100-µM desferrioxamine mesylate salt for 24h, to mimic the hypoxic stress affecting motor neurons during the disease progression. Our results showed that PACAP treatment significantly reduced cell death and hypoxia-induced mSOD1 accumulation by modulating the autophagy process in G93A motor neurons, as revealed by the decreased LC3II and the increased p62 levels, two autophagy indicators. These results were also confirmed by evaluating the vacuole formation detected through light chain 3 (LC3) immunofluorescence. Furthermore, the PACAP effects on autophagy seem to be mediated through the activation of the MAPK/ERK signaling pathway. Overall, our data demonstrated that PACAP exerts an ameliorative effect on the mSOD1 motor neuron viability by modulating a hypoxia-induced autophagy process through activation of MAPK/ERK signaling cascade.

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n‐butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in SOD1^G93A mouse model of amyotrophic lateral sclerosis

Abstract: Our study suggests that BP may be a promising candidate for the treatment of ALS.

Cited by 37 publications

References 45 publications

Repurposing carbamazepine for the treatment of amyotrophic lateral sclerosis in SOD1‐G93A mouse model

Repurposing carbamazepine for the treatment of amyotrophic lateral sclerosis in SOD1‐G93A mouse model

Role of Neuroinflammation in Amyotrophic Lateral Sclerosis: Cellular Mechanisms and Therapeutic Implications

PACAP Modulates the Autophagy Process in an In Vitro Model of Amyotrophic Lateral Sclerosis

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n‐butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in SOD1G93A mouse model of amyotrophic lateral sclerosis

Abstract: Our study suggests that BP may be a promising candidate for the treatment of ALS.

Cited by 37 publications

References 45 publications

Repurposing carbamazepine for the treatment of amyotrophic lateral sclerosis in SOD1‐G93A mouse model

Repurposing carbamazepine for the treatment of amyotrophic lateral sclerosis in SOD1‐G93A mouse model

Role of Neuroinflammation in Amyotrophic Lateral Sclerosis: Cellular Mechanisms and Therapeutic Implications

PACAP Modulates the Autophagy Process in an In Vitro Model of Amyotrophic Lateral Sclerosis

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Product

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n‐butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in SOD1^G93A mouse model of amyotrophic lateral sclerosis