scholarly journals Role of Cdk5rap2 in neocortical inhibition and excitation balance

2020 ◽  
Author(s):  
Sami Zaqout ◽  
Lena-Luise Becker ◽  
Ayman Mustafa ◽  
Nadine Krame ◽  
Ulf Strauss ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Brain Size ◽  
Regulatory Subunit ◽  
Cyclin Dependent Kinase ◽  
Congenital Microcephaly ◽  
Biallelic Mutations ◽  
Type 3 ◽  
Autosomal Recessive Primary Microcephaly ◽  
Cyclin Dependent Kinase 5

Autosomal recessive primary microcephaly type 3 (MCPH3) is characterized by congenital microcephaly and intellectual disability. Further features include hyperactivity and seizures. The disease is caused by biallelic mutations in the Cyclin-dependent kinase 5 regulatory subunit-associated protein 2 gene CDK5RAP2. In the mouse, Cdk5rap2 mutations similarly result in reduced brain size and a strikingly thin neocortex already at early stages of neurogenesis that persists through adulthood. The microcephaly phenotype in MCPH arises from a neural stem cell proliferation defect. Here, we report a novel role for Cdk5rap2 in the regulation of dendritic development and synaptogenesis of neocortical layer 2/3 pyramidal neurons using a combined morphological and electrophysiological approach

Role of cyclin-dependent kinase 5 in capsaicin-induced cough

2007 ◽  
Vol 566 (1-3) ◽  
pp. 181-184 ◽  
Author(s):  
Junzo Kamei ◽  
Shun-suke Hayashi ◽  
Yoshiki Takahashi ◽  
Chihiro Nozaki
Keyword(s):  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase 5

Alzheimer Disease and Related Tauopathies: Possible Neuroprotective Strategies

2018 ◽  
Vol 2 (3) ◽  
pp. 01-02
Author(s):  
Meketa Muñoz
Keyword(s):  
Alzheimer Disease ◽  
Glycogen Synthase ◽  
Vital Role ◽  
Current Therapy ◽  
Cyclin Dependent Kinase ◽  
Abnormal Hyperphosphorylation ◽  
Neuroprotective Strategies ◽  
Gsk 3Β ◽  
Cyclin Dependent Kinase 5

Alzheimer disease (AD) is the most common cause of dementia in adults. The current therapy for AD has only moderate efficacy in controlling symptoms, and it does not cure the disease. Recent studies have suggested that abnormal hyperphosphorylation of tau in the brain plays a vital role in the molecular pathogenesis of AD and in neurodegeneration. This article reviews the current advances in understanding of tau protein, regulation of tau phosphorylation, and the role of its abnormal hyperphosphorylation in neurofibrillary degeneration. Furthermore, several therapeutic strategies for treating AD on the basis of the important role of tau hyperphosphorylation in the pathogenesis of the disease are described. These strategies include (1) inhibition of glycogen synthase kinase-3β (GSK-3β), cyclin-dependent kinase 5 (cdk5), and other tau kinases; (2) restoration of PP2A activity; and (3) targeting tau O-GlcNAcylation. Development of drugs on the basis of these strategies is likely to lead to disease-modifying therapies for AD.

scholarly journals Down-regulation of cyclin-dependent kinase 5 attenuates p53-dependent apoptosis of hippocampal CA1 pyramidal neurons following transient cerebral ischemia

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bich Na Shin ◽  
Dae Won Kim ◽  
In Hye Kim ◽  
Joon Ha Park ◽  
Ji Hyeon Ahn ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Caspase 3 ◽  
Pyramidal Neurons ◽  
Transient Cerebral Ischemia ◽  
Cyclin Dependent Kinase ◽  
Neuroprotective Effects ◽  
Expression Levels ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
Cyclin Dependent Kinase 5

Abstract Abnormal activation of cyclin-dependent kinase 5 (Cdk5) is associated with pathophysiological conditions. Ischemic preconditioning (IPC) can provide neuroprotective effects against subsequent lethal ischemic insult. The objective of this study was to determine how Cdk5 and related molecules could affect neuroprotection in the hippocampus of gerbils after with IPC [a 2-min transient cerebral ischemia (TCI)] followed by 5-min subsequent TCI. Hippocampal CA1 pyramidal neurons were dead at 5 days post-TCI. However, treatment with roscovitine (a potent inhibitor of Cdk5) and IPC protected CA1 pyramidal neurons from TCI. Expression levels of Cdk5, p25, phospho (p)-Rb and p-p53 were increased in nuclei of CA1 pyramidal neurons at 1 and 2 days after TCI. However, these expressions were attenuated by roscovitine treatment and IPC. In particular, Cdk5, p-Rb and p-p53 immunoreactivities in their nuclei were decreased. Furthermore, TUNEL-positive CA1 pyramidal neurons were found at 5 days after TCI with increased expression levels of Bax, PUMA, and activated caspase-3. These TUNEL-positive cells and increased molecules were decreased by roscovitine treatment and IPC. Thus, roscovitine treatment and IPC could protect CA1 pyramidal neurons from TCI through down-regulating Cdk5, p25, and p-p53 in their nuclei. These findings indicate that down-regulating Cdk5 might be a key strategy to attenuate p53-dependent apoptosis of CA1 pyramidal neurons following TCI.

Is there a role of the cyclin-dependent kinase 5 activator p25 in Alzheimer??s disease?

Neuroreport ◽  
2005 ◽  
Vol 16 (16) ◽  
pp. 1725-1730 ◽  
Author(s):  
K. Peter Giese ◽  
Laurence Ris ◽  
Florian Plattner
Keyword(s):  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase 5

scholarly journals Phosphatase 2A Negatively Regulates Mitotic Exit in Saccharomyces cerevisiae

2006 ◽  
Vol 17 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Yanchang Wang ◽  
Tuen-Yung Ng
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mitotic Exit ◽  
Regulatory Subunit ◽  
Temperature Sensitive ◽  
Cyclin Dependent Kinase ◽  
Yeast Saccharomyces Cerevisiae ◽  
Catalytic Subunits ◽  
Phosphatase 2A ◽  
Negative Role

In budding yeast Saccharomyces cerevisiae, Cdc5 kinase is a component of mitotic exit network (MEN), which inactivates cyclin-dependent kinase (CDK) after chromosome segregation. cdc5-1 mutants arrest at telophase at the nonpermissive temperature due to the failure of CDK inactivation. To identify more negative regulators of MEN, we carried out a genetic screen for genes that are toxic to cdc5-1 mutants when overexpressed. Genes that encode the B-regulatory subunit (Cdc55) and the three catalytic subunits (Pph21, Pph22, and Pph3) of phosphatase 2A (PP2A) were isolated. In addition to cdc5-1, overexpression of CDC55, PPH21, or PPH22 is also toxic to other temperature-sensitive mutants that display defects in mitotic exit. Consistently, deletion of CDC55 partially suppresses the temperature sensitivity of these mutants. Moreover, in the presence of spindle damage, PP2A mutants display nuclear localized Cdc14, the key player in MEN pathway, indicative of MEN activation. All the evidence suggests the negative role of PP2A in mitotic exit. Finally, our genetic and biochemical data suggest that PP2A regulates the phosphorylation of Tem1, which acts at the very top of MEN pathway.

scholarly journals Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Guo-Qiang Wang ◽  
Cheng Cen ◽  
Chong Li ◽  
Shuai Cao ◽  
Ning Wang ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Prelimbic Cortex ◽  
Cyclin Dependent Kinase ◽  
Pain Sensation ◽  
Pain Model ◽  
Excitatory Neurons ◽  
Affective Pain ◽  
Underlying Mechanisms ◽  
Cyclin Dependent Kinase 5

Abstract The medial prefrontal cortex (mPFC) is implicated in processing sensory-discriminative and affective pain. Nonetheless, the underlying mechanisms are poorly understood. Here we demonstrate a role for excitatory neurons in the prelimbic cortex (PL), a sub-region of mPFC, in the regulation of pain sensation and anxiety-like behaviours. Using a chronic inflammatory pain model, we show that lesion of the PL contralateral but not ipsilateral to the inflamed paw attenuates hyperalgesia and anxiety-like behaviours in rats. Optogenetic activation of contralateral PL excitatory neurons exerts analgesic and anxiolytic effects in mice subjected to chronic pain, whereas inhibition is anxiogenic in naive mice. The intrinsic excitability of contralateral PL excitatory neurons is decreased in chronic pain rats; knocking down cyclin-dependent kinase 5 reverses this deactivation and alleviates behavioural impairments. Together, our findings provide novel insights into the role of PL excitatory neurons in the regulation of sensory and affective pain.

scholarly journals The role of cyclin-dependent kinase 5 in neuropathic pain

Pain ◽  
2020 ◽  
Vol 161 (12) ◽  
pp. 2674-2689 ◽  
Author(s):  
Kimberly Gomez ◽  
Tissiana G.M. Vallecillo ◽  
Aubin Moutal ◽  
Samantha Perez-Miller ◽  
Rodolfo Delgado-Lezama ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase 5
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