p(HBP:"CDK5R1 p25")

Entity

Name

CDK5R1 p25

Namespace

HBP

Namespace Version

20181119

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/90e1cb9e5e882703380c9db8d4915ac6f3cba137/export/hbp-names.belns

We demonstrated that the treatment of cultured hippocampal neurons with 125 µM glutamate for 20 min induced the cleavage of p35 to produce the p25 fragment 6 h after glutamate treatment, and the maximal levels of p25 were detected at 12 h (Fig. 1A), which is consistent with a peak in tau hyperphosphorylation (AT8). PubMed:27087442

The accumulation of p25 involves neurofibrillary tangle (NFT) formation via regulation of tau phosphorylation (Wen et al. 2007; Su and Tsai 2011) PubMed:26118667

We observed that 2VO leads to tau hyperphosphorylation at Ser202/Thr205, Ser262, Thr231, and Ser422 and to the conversion from cyclin-dependent kinase 5 (Cdk5)/p35 to Cdk5/p25 in rat hippocampi. PubMed:26118667

Small molecules in the diaminothiazole class are potent Tau kinase inhibitors that target CDK5 and GSK3β. Lead compounds from the series have IC50 values toward CDK5/p25 and GSK3β in the low nanomolar range and no observed toxicity in the therapeutic dose range. Neuronal protective effects and decreased PHF-1 immunoreactivity were observed in two animal models, 3×Tg-AD and CK-p25. Treatment nearly eliminated Sarkosyl-insoluble Tau with the most prominent effect on the phosphorylation at Ser-404. Treatment also induced the recovery of memory in a fear conditioning assay. PubMed:23737518

To perform its function, Cdk5 must bind to the neuron-specific regulatory subunit protein p35, which is beneficial for neuronal development (Tsai et al. 1994; Chae et al. 1997). However, truncation of p35 and conversion to p25 (Patrick et al. 1999) is found in the forebrain of rats after focal cerebral ischemia and in AD patients, and these alterations are deleterious to the brain PubMed:26118667

Primary cortical neurons exposed to the mitochondrial toxin NaN3 (0.1-3 mM) were submitted to oxidative stress with H2O2 (30-150 μM), to mimic conditions observed in neurodegenerative disorders. The effects of such treatment on a series of parameters useful in characterizing neuronal damage were investigated: (i) the basal release of glutamate, evaluated as (3)H-d-Aspartate efflux, was sharply, concentration-dependently, increased; (ii) the phosphorylation status of intracellular markers known to be involved in the neurodegenerative processes, in particular in Alzheimer disease: tau and GSK3β were increased, as well as the protein level of β-secretase (BACE1) and p35/25 evaluated by Western blotting, while (iii) the cell metabolic activity, measured with the MTT method, was reduced, in a concentration- and time-dependent manner. The latter effect, as well as tau hyperphosphorylation, was prevented both by a mixture of antioxidant drugs (100 μM ascorbic acid, 10 μM trolox, 100 μM glutathione) and by the anti-Alzheimer drug, memantine, 20 μM. PubMed:23722080

The levels of CDK5, its regulatory subunits (p35 and p25) and calpain (including calpain1 and calpain2), but not GSK3ß, were significantly increased in E4FAD mice compared to E3FAD mice. PubMed:27087442

We demonstrated that the treatment of cultured hippocampal neurons with 125 µM glutamate for 20 min induced the cleavage of p35 to produce the p25 fragment 6 h after glutamate treatment, and the maximal levels of p25 were detected at 12 h (Fig. 1A), which is consistent with a peak in tau hyperphosphorylation (AT8). PubMed:27087442

To perform its function, Cdk5 must bind to the neuron-specific regulatory subunit protein p35, which is beneficial for neuronal development (Tsai et al. 1994; Chae et al. 1997). However, truncation of p35 and conversion to p25 (Patrick et al. 1999) is found in the forebrain of rats after focal cerebral ischemia and in AD patients, and these alterations are deleterious to the brain PubMed:26118667

Tau peptides containing phosphorylated S202, T205, and T396 were found only in Tg mice, supporting our results using AT8 and PHF1 antibodies PubMed:14642273

Tau peptides containing phosphorylated S202, T205, and T396 were found only in Tg mice, supporting our results using AT8 and PHF1 antibodies PubMed:14642273

To perform its function, Cdk5 must bind to the neuron-specific regulatory subunit protein p35, which is beneficial for neuronal development (Tsai et al. 1994; Chae et al. 1997). However, truncation of p35 and conversion to p25 (Patrick et al. 1999) is found in the forebrain of rats after focal cerebral ischemia and in AD patients, and these alterations are deleterious to the brain PubMed:26118667

To perform its function, Cdk5 must bind to the neuron-specific regulatory subunit protein p35, which is beneficial for neuronal development (Tsai et al. 1994; Chae et al. 1997). However, truncation of p35 and conversion to p25 (Patrick et al. 1999) is found in the forebrain of rats after focal cerebral ischemia and in AD patients, and these alterations are deleterious to the brain PubMed:26118667

The accumulation of p25 involves neurofibrillary tangle (NFT) formation via regulation of tau phosphorylation (Wen et al. 2007; Su and Tsai 2011) PubMed:26118667

We demonstrated that the treatment of cultured hippocampal neurons with 125 µM glutamate for 20 min induced the cleavage of p35 to produce the p25 fragment 6 h after glutamate treatment, and the maximal levels of p25 were detected at 12 h (Fig. 1A), which is consistent with a peak in tau hyperphosphorylation (AT8). PubMed:27087442