Crmp-2

The collapsin response mediator protein (CRMP-2) is hyperphosphorylated in Alzheimer's disease (AD). These phosphorylation events are mediated by specific kinase proteins, GSK3β and Cdk5, and occur at target phosphorylation sites majorly located at the C-terminal tail of CRMP-2. The abilities of naringenin (NAR) and naringenin-7-O-glucuronide (NAR-7-O-G) to selectively bind CRMP-2 and reduce its phosphorylation have been previously demonstrated; the molecular interplay between these events remains unresolved...

Early neurodevelopmental dysplasia or disorder is an important stimulus for depression, but early stress can easily damage nerve development and lead to decreased neural plasticity. Because of the characteristics of nerve cell, nerve loop, structure instability and so on, stress can often lead to the occurrence and recurrence of depression. Stress is often associated with the release of inflammatory factors in the central nervous system. Recent studies suggest that neuroinflammatory factors are most likely involved in the occurrence and development of stress-induced depression, attacking neuronal cells through central inflammatory factors...

BACKGROUND Collapsin response mediator protein-2 (CRMP-2) is the first member of the CRMP family that has been identified in primary neuronal cells; it was originally found and identified in the regulation of microtubule dimerization into microtubules. MATERIAL AND METHODS In the present study, we aimed to investigate the roles and mechanisms of CRMP-2 in sevoflurane-induced neurocyte injury. Cell viability, proliferation, and apoptosis were measured by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Colorimetry was performed to measure the activity of caspase-3...

OBJECTIVE: Currently, lacosamide (LCM) is not approved for use in status epilepticus (SE) but several shreds of evidence are available to support its use. The present study was, therefore, undertaken to evaluate the effect of LCM on pilocarpine (PILO) induced SE and neurodegeneration in C57BL/6 mice and to ascertain the involvement of CRMP-2 in mediating above effect. METHODS: Pilocarpine-induced SE model was developed to explore the effect of LCM 20, 40 and 80 mg/kg in mice...

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by accumulation of amyloid plaques and neurofibrillary tangles. Prior to the development of these characteristic pathological hallmarks of AD, anterograde axonal transport is impaired. However, the key proteins that initiate these intracellular impairments remain elusive. The collapsin response mediator protein-2 (CRMP-2) plays an integral role in kinesin-1-dependent axonal transport and there is evidence that phosphorylation of CRMP-2 releases kinesin-1...

The discovery and developmental processes of CNS drugs have been limited by the inability of potential drug molecules to pass through the blood-brain barrier (BBB). This presents a significant setback in the treatment of neurodegenerative disorders such as Alzheimer's disease (AD), hence the need for compounds that can adhere strictly to the selective criteria of suitable CNS drugs. Collapsin response mediator protein-2 (CRMP-2) has been recently identified as a viable target in neurotherapeutics due to its involvement in the etiology of AD...

Prolonged exposure to volatile anesthetics causes neurodegeneration in developing animal brains. However, their underlying mechanisms of action remain unclear. The current study investigated the expression of proteins associated with the mitogen-activated protein kinases (MAPK) and protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β)/collapsin response mediator protein 2 (CRMP-2) signaling pathways in the cortices of neonatal mice following exposure to sevoflurane. Seven-day-old (P7) neonatal C57BL/6 mice were randomly divided into 2 groups and either exposed to 2...

Collapsin response mediator protein (CRMP)-2 and the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway are associated with common physiological functions such as neuronal polarity, axonal outgrowth and synaptic strength, as well as various brain disorders including epilepsy. But, their regulatory and functional links are unclear. Alterations in CRMP-2 expression that lead to its functional changes are implicated in brain disorders such as epilepsy. Here, we investigate whether changes in CRMP-2 expression, possibly regulated by mTOR-related signaling, correlates with neuronal growth and viability...

Moderate physical exercise acts at molecular and behavioural levels, such as interfering in neuroplasticity, cell death, neurogenesis, cognition and motor functions. Therefore, the aim of this study is to analyse the cellular effects of moderate treadmill running upon substantia nigra during early neurodegeneration. Aged male Lewis rats (9-month-old) were exposed to rotenone 1mg/kg/day (8 weeks) and 6 weeks of moderate treadmill running, beginning 4 weeks after rotenone exposure. Substantia nigra was extracted and submitted to proteasome and antioxidant enzymes activities, hydrogen peroxide levels and Western blot to evaluate tyrosine hydroxylase (TH), alpha-synuclein, Tom-20, PINK1, TrkB, SLP1, CRMP-2, Rab-27b, LC3II and Beclin-1 level...

Collapsin response mediator protein-2 (CRMP-2) is involved in neurite elongation and regeneration; however, its role in wound healing remains to be elucidated. The present study aimed to investigate the effects of active mobilization treatment on Achilles tendon healing and to determine the role of CRMP‑2 in the healing process. Sprague Dawley rats were subjected to Achilles tendon injury, which was verified by hematoxylin and eosin staining and scanning electronic microscopy. Immobilization induced the disruption of collagen fibril arrangement and promoted collagen fibril damage...

Neurite growth is an important process for the adult hippocampal neurogenesis which is regulated by a specific range of the intracellular free Ca(2+) concentration ([Ca(2+)]i). Transient receptor potential vanilloid 4 (TRPV4) is a calcium-permeable channel and activation of it causes an increase in [Ca(2+)]i. We recently reported that TRPV4 activation promotes the proliferation of stem cells in the adult hippocampal dentate gyrus (DG). The present study aimed to examine the effect of TRPV4 activation on the dendrite morphology of newborn neurons in the adult hippocampal DG...

Long-range anterograde axonal transport of TrkB is important for neurons to exert appropriate BDNF responses. TrkB anterograde axonal delivery is mediated by kinesin-1, which associates with TrkB via the adaptor protein JIP3 or the Slp1/Rab27B/CRMP-2 protein complex. However, little is known about the activation mechanisms of TrkB-loaded kinesin-1. Here, we show that JIP1 mediates TrkB anterograde axonal transport using JIP1 knockout mice, sciatic nerve ligation analysis and live imaging. Next, we proved that JIP1 and JIP3 cooperate to mediate TrkB anterograde axonal transport...

Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes...

Collapsin response mediator protein 2 (CRMP-2) is a neuronal protein involved in axonal pathfinding. Intense research is focusing on its role in various neurological diseases. Despite a wealth of studies, not much is known about the molecular mechanisms of CRMP-2 function in vivo. The detailed structure-function relationships of CRMP-2 have also largely remained unknown, in part due to the fact that the available crystal structures lack the C-terminal tail, which is known to be a target for many post-translational modifications and protein interactions...

OBJECTIVE: Preeclampsia (PE) is pregnancy-induced hypertension with proteinuria. It causes maternal death or fetal growth restriction (FGR). Although high BP can be managed with antihypertensive drugs, there is no effective treatment of FGR associated with PE. We have clarified that nicotinamide (Nam) alleviates PE-like condition and FGR induced by soluble fms-like tyrosine kinase-1 (sFlt-1) in mice. But the mechanism of how Nam works is unclear. Because Nam induces cytoprotective heme oxygenase 1 (HO-1), our aim is to clarify whether HO-1 contributes to therapeutic effect of Nam against FGR associated with PE...

OBJECTIVE: Preeclampsia (PE) is pregnancy-induced hypertension with proteinuria. It causes maternal death or fetal growth restriction (FGR). Although high BP can be managed with antihypertensive drugs, there is no effective treatment of FGR associated with PE. We have clarified that nicotinamide (Nam) alleviates PE-like condition and FGR induced by soluble fms-like tyrosine kinase-1 (sFlt-1) in mice. But the mechanism of how Nam works is unclear. Because Nam induces cytoprotective heme oxygenase 1 (HO-1), our aim is to clarify whether HO-1 contributes to therapeutic effect of Nam against FGR associated with PE...

Mammalian target of rapamycin complex 1 (mTORC1) has an essential role in dendritic mRNA translation and participates in mechanisms underlying alcohol-drinking and reconsolidation of alcohol-related memories. Here, we report that excessive alcohol consumption increases the translation of downstream targets of mTORC1, including collapsin response mediator protein-2 (CRMP-2), in the nucleus accumbens (NAc) of rodents. We show that alcohol-mediated induction of CRMP-2 translation is mTORC1-dependent, leading to increased CRMP-2 protein levels...

Central post-stroke pain (CPSP) is one of the complications of cerebral ischemia and neuropathic pain syndrome. At present, there are few studies of pain in regions such as the spinal cord or sciatic nerve in cerebral ischemic animal models. To identify proteomic changes in the spinal cord and sciatic nerve in global cerebral ischemic model mice, in the present study we performed an investigation using proteomic methods. In a comparison between the intensity of protein spots obtained from a sham and that from a bilateral carotid artery occulusion (BCAO) in spinal cord and sciatic nerve, the levels of 10 (spinal cord) and 7 (sciatic nerve) protein spots were altered...

The use of early mobilization of the ankle joint without orthosis in the treatment of Achilles tendon rupture has been advocated as the optimal management. The goal of this study was to compare outcomes in a postoperative rabbit model of Achilles tendon rupture between early mobilization and immobilized animals using a differential proteomics approach. In total, 135 rabbits were randomized into the control group (n=15), the postoperative cast immobilization (PCI) group (n=60), and the early mobilization (EM) group (n=60)...

Several reports have linked the presence of high titers of anti-Gg Abs with delayed recovery/poor prognosis in GBS. In most cases, failure to recover is associated with halted/deficient axon regeneration. Previous work identified that monoclonal and patient-derived anti-Gg Abs can act as inhibitory factors in an animal model of axon regeneration. Further studies using primary dorsal root ganglion neuron (DRGn) cultures demonstrated that anti-Gg Abs can inhibit neurite outgrowth by targeting gangliosides via activation of the small GTPase RhoA and its associated kinase (ROCK), a signaling pathway common to other established inhibitors of axon regeneration...