What is tfp5

View 1 excerpt, references background. Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. View 2 excerpts, references background. Overexpression of p35 in Min6 pancreatic beta cells induces a stressed neuron-like apoptosis. View 3 excerpts, references background. Cdk5 deregulation in the pathogenesis of Alzheimer's disease. A peptide derived from cyclin-dependent kinase activator p35 specifically inhibits Cdk5 activity and phosphorylation of tau protein in transfected cells.

Related Papers. Kinase assays were performed as described previously, with modification Binukumar et al. Histone bands were visualized by Coomassie blue staining. Gels were dried, and then autoradiographs were scanned on a PhosphorImager. After air-drying, squares were transferred to vials containing Bio-Safe II scintillation fluid for counting.

Mice were allowed free access to food and water. Use of the animals and protocol procedures were approved and supervised by Institutional Animal Care. The following groups of animals were used in most experiments:.

Western blot analysis was performed as described previously Binukumar et al. Ten-micrometer cryostat sections of midbrain and substantia nigra were collected on slides and prepared for immunohistochemistry, which was performed according to standard protocols for single or double immunostaining Wu et al.

Immunostaining was visualized by fluorescein and Texas red secondary antibodies Vector Laboratories and was examined by transmitted or confocal microscopy. The striatal density of TH immunoreactivity was determined as described Bifsha et al. To quantify dopamine neuron degeneration, cell counts were performed using ImageJ.

For cell counts of degenerating neurons, TH-stained coronal sections were loaded on ImageJ; the sections spanned regular intervals 30 or mm across the rostrocaudal extent of midbrains of three mice each in the different groups. Statistical significance was calculated using analysis of variance Bifsha et al.

The infrared monitoring sensors were located every 2. Two additional sets of 16 sensors were located 8. Before any treatment, mice were placed inside the infrared monitor for 10 min daily for three consecutive days to train them. At 16 and 48 h after the last MPTP injection, open-field experiments were conducted. In the open-field experiment, mice were monitored for horizontal activity, vertical activity, total distance traveled centimeters , total movement time seconds , total rest time seconds , and rearing activity over a min test session.

We used Versaplot and Versadat software to analyze the data among the four groups. Absolute concentrations were derived by comparison with a standard curve.

Data were analyzed with Prism 3. Bonferroni and Dunnett multiple comparison testing was used. E on September 23, This article is distributed by The American Society for Cell Biology under license from the author s. Two months after publication it is available to the public under an Attribution—Noncommercial—Share Alike 3. Molecular Biology of the Cell Vol. This is the final version - click for previous version.

Niranjana D. Harish C. Pant 1 Address correspondence to: Harish C. Add to favorites Download Citations Track Citations. View article. Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5. Cyclin-dependent kinase 5 cdk5 activation requires interaction with three domains of p J Neurosci Res 67 , — Rgs6 is required for adult maintenance of dopaminergic neurons in the ventral substantia nigra.

TFP5, a peptide derived from p35, a Cdk5 neuronal activator, rescues cortical neurons from glucose toxicity. J Alzheimers Dis 39 , — Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8 , 57— Cortical and brainstem-type Lewy bodies are immunoreactive for the cyclin-dependent kinase 5.

Am J Pathol , — J Neural Transm Gen Sect , — Cdk5: mediator of neuronal death and survival. Neurosci Lett , 47— Cannabinoid receptor type 1 protects nigrostriatal dopaminergic neurons against MPTP neurotoxicity by inhibiting microglial activation. J Immunol , — Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition. Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles.

Neuron 40 , — The Parkinson disease mitochondrial hypothesis: where are we at. J Neural Transm , — J Neurochem 81 , — Commitment to apoptosis by ceramides depends on mitochondrial respiratory function, cytochrome c release and caspase-3 activation in Hep-G2 cells.

Mol Cell Biochem , — The peptidyl-prolyl isomerase Pin1 up-regulation and proapoptotic function in dopaminergic neurons: relevance to the pathogenesis of Parkinson disease. Chung YC, Kim SR, Jin BK Paroxetine prevents loss of nigrostriatal dopaminergic neurons by inhibiting brain inflammation and oxidative stress in an experimental model of Parkinson's disease. J Immunol J Neuroinflammation Grant P, Pant HC Topographic regulation of phosphorylation in giant neurons of the squid, Loligo pealei: role of phosphatases.

J Neurobiol J Comp Neurol Neuron Biotechnol J Nat Med Acta Neuropathol Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature Biochemistry A truncated peptide from p35, a Cdk5 activator, prevents Alzheimer's disease phenotypes in model mice. Whether TFP5 is able to penetrate through cell membranes following application to cultured primary neurons was investigated. The neurons were observed with a fluorescence microscope 3 h after the application of TFP5.

As indicated in Fig. Thus, TFP5, with FITC as a fused fluorescence label, successfully penetrated through the cell membranes of primary mouse cortical neurons.

TFP5 distribution in cultured neurons. B Fluorescence microscopy of primary mouse cortical neurons to which 0. TFP5 green fluorescence penetrated the cell membrane and was located in cytoplasm of the neurons at 3 h after application to the culture. Therefore, it may be hypothesized that p5 could play the same role in a PD model.

The results showed that TFP5 was able to penetrate the cell membrane of neurons and was distributed around the nucleus.

The results of the present study indicate that TFP5 reduced the hyperphosphorylation of MEF2D and thus may have prevented neuronal apoptosis. Inflammatory factors also play an important role in the pathology of PD.

In conclusion, the findings of the present study provide new information that increases our understanding of the neuroprotective role of TFP5 and its potential for use in clinical trials. This study was supported by grants from the Nature Science Foundation of Guangdong Province grant no.

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