Neuroprotection Exerted by Netrin-1 and Kinesin Motor KIF1A in Secondary Brain Injury following Experimental Intracerebral Hemorrhage in Rats

Wang, Jun; Zhai, Weiwei; Yu, Zhengquan; Sun, Liang; Li, Haiying; Shen, Haitao; Li, Xiang; Liu, Chun‐Feng; Chen, Gang

doi:10.3389/fncel.2017.00432

Cited by 14 publications

(10 citation statements)

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“…Whether netrin-1 is packaged within DCVs is currently unknown. However, UNC-104/KIF1A has been implicated in trafficking of its homologue UNC-6 in C. elegans (Ogura et al, 2012) and in rats with intracerebral hemorrhage, KIF1A abolishment led to attenuation of netrin-1-related functions (Wang et al, 2018). Notably, netrin-1 seems to be critical for guidance of CST axons, particularly within the pyramidal decussation and dorsal funiculus as netrin-1 mutant mice show defects in these regions (Finger et al, 2002).…”

Section: Kif1a Cargosmentioning

confidence: 99%

Going Too Far Is the Same as Falling Short†: Kinesin-3 Family Members in Hereditary Spastic Paraplegia

Gabrych

Lau

Niwa

et al. 2019

Front. Cell. Neurosci.

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Proper intracellular trafficking is essential for neuronal development and function, and when any aspect of this process is dysregulated, the resulting “transportopathy” causes neurological disorders. Hereditary spastic paraplegias (HSPs) are a family of such diseases attributed to over 80 spastic gait genes (SPG), specifically characterized by lower extremity spasticity and weakness. Multiple genes in the trafficking pathway such as those relating to microtubule structure and function and organelle biogenesis are representative disease loci. Microtubule motor proteins, or kinesins, are also causal in HSP, specifically mutations in Kinesin-I/KIF5A (SPG10) and two kinesin-3 family members; KIF1A (SPG30) and KIF1C (SPG58). KIF1A is a motor enriched in neurons, and involved in the anterograde transport of a variety of vesicles that contribute to pre- and post-synaptic assembly, autophagic processes, and neuron survival. KIF1C is ubiquitously expressed and, in addition to anterograde cargo transport, also functions in retrograde transport between the Golgi and the endoplasmic reticulum. Only a handful of KIF1C cargos have been identified; however, many have crucial roles such as neuronal differentiation, outgrowth, plasticity and survival. HSP-related kinesin-3 mutants are characterized mainly as loss-of-function resulting in deficits in motility, regulation, and cargo binding. Gain-of-function mutants are also seen, and are characterized by increased microtubule-on rates and hypermotility. Both sets of mutations ultimately result in misdelivery of critical cargos within the neuron. This likely leads to deleterious cell biological cascades that likely underlie or contribute to HSP clinical pathology and ultimately, symptomology. Due to the paucity of histopathological or cell biological data assessing perturbations in cargo localization, it has been difficult to positively link these mutations to the outcomes seen in HSPs. Ultimately, the goal of this review is to encourage future academic and clinical efforts to focus on “transportopathies” through a cargo-centric lens.

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Section: Kif1a Cargosmentioning

confidence: 99%

Going Too Far Is the Same as Falling Short†: Kinesin-3 Family Members in Hereditary Spastic Paraplegia

Gabrych

Lau

Niwa

et al. 2019

Front. Cell. Neurosci.

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“…Immunohistochemistry and immunofluorescence experiments were performed as previously described (Wang et al., 2017 ). In brief, paraffin-embedded coronal brain sections (10 μm) from 4 to 5 animals in each group were prepared, with the operation site near the hippocampus being the main target sampling area.…”

Section: Methodsmentioning

confidence: 99%

Intranasal administration of dauricine loaded on graphene oxide: multi-target therapy for Alzheimer's disease

Wang

Chen

et al. 2021

Drug Delivery

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Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by progressive cognitive and memory-related impairment. However, current therapeutic treatments have not proved sufficiently effective, mainly due to the complicated pathogenesis of the disease. In this study, a nano-formulation of graphene oxide (GO) loaded with dauricine (Dau) was investigated in terms of the combined anti-inflammatory and anti-oxidative stress effects of Dau and the inhibition of misfolding and aggregation of the amyloid-β (Aβ) protein by GO. Both in vivo and in vitro models were induced using Aβ 1-42 , and the formulation was administered nasally in mice. The results showed that GO loaded with Dau greatly reduced oxidative stress through increasing superoxide dismutase levels and decreasing reactive oxygen species and malondialdehyde levels in vitro ; it also alleviated the cognitive memory deficits and brain glial cell activation in mice with Aβ 1-42 -induced AD. This proved that GO loaded with Dau could protect against Aβ 1-42 -induced oxidative damage and apoptosis in both in vitro and in vivo AD models; therefore, GO loaded with Dau has the potential to be an effective and agent for the rapid treatment of AD.

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“…An exogenous administration of netrin-1 also protected against brain injury by activation of anti-apoptotic mechanisms. In addition, netrin-1 preserved blood–brain barrier integrity in SAH (Xie et al, 2017a,c), diminished brain injury secondary to stroke (Wu et al, 2008; Liao et al, 2013; Yu et al, 2017) and intracerebral hemorrhage (Wang et al, 2017). In animal models of AD, netrin-1 has been reported to reduce Aβ 1–40 -induced Aβ 1–42 increases, as demonstrated in vitro , and decrease both Aβ 1–40 and Aβ 1–42 in PDAPP Swe/Ind transgenic mice, effects which were accompanied with improved working memory (Spilman et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Decreased Netrin-1 and Correlated Th17/Tregs Balance Disorder in Aβ1–42 Induced Alzheimer’s Disease Model Rats

Sun

Wang

et al. 2019

Front. Aging Neurosci.

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There is increasing evidence indicating that inflammation represents a key pathological component of Alzheimer’s disease (AD). A possible factor that may contribute to this process is netrin-1, a neuronal guidance molecule. This molecule has been shown to exert an unexpected immunomodulatory function. However, the potential changes and correlations of netrin-1 with T helper 17/regulatory T cells (Th17/Tregs) as related to inflammation in AD has yet to be examined. In this study, netrin-1 and Th17/Tregs balance were investigated, and the relationship among netrin-1, Th17/Tregs and cognitive function were analyzed in a rat model of AD. In this model, a bilateral intracerebroventricular administration of Amyloid β 1-42 (Aβ 1–42 ) was used to produce spatial learning and memory deficits, as well as increased neuronal apoptosis, which were detected 7 days after injection for AD7d group and 14 days for AD14d group. Netrin-1 concentrations were significantly down regulated in both serum and cerebrospinal fluid (CSF) of these AD rats, effects which were strongly correlated with cognitive deficits. Increased levels of interleukin (IL)-17 and deceased IL-10 were observed in both the circulation and CSF and were also correlated with the percent of time spent in the target quadrant of AD in these rats. These changes resulted in netrin-1 concentrations being negatively correlated with IL-17 but positively correlated with IL-10 concentrations in the serum and CSF. We also found that the Th17/Tregs balance was disrupted in these AD rats. Collectively, these findings reveal that the reduction in netrin-1 and the correlated disruption of Th17/Tregs balance in AD rats may diminish the immunosuppressive effect of netrin-1 on Th17/Tregs in AD pathogenesis.

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Neuroprotection Exerted by Netrin-1 and Kinesin Motor KIF1A in Secondary Brain Injury following Experimental Intracerebral Hemorrhage in Rats

Cited by 14 publications

References 50 publications

Going Too Far Is the Same as Falling Short†: Kinesin-3 Family Members in Hereditary Spastic Paraplegia

Going Too Far Is the Same as Falling Short†: Kinesin-3 Family Members in Hereditary Spastic Paraplegia

Intranasal administration of dauricine loaded on graphene oxide: multi-target therapy for Alzheimer's disease

Decreased Netrin-1 and Correlated Th17/Tregs Balance Disorder in Aβ1–42 Induced Alzheimer’s Disease Model Rats

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