Limits...
Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson's disease.

Binukumar BK, Shukla V, Amin ND, Grant P, Bhaskar M, Skuntz S, Steiner J, Pant HC - Mol. Biol. Cell (2015)

Bottom Line: To date, strategies to specifically inhibit Cdk5 hyperactivity have not been successful without affecting normal Cdk5 activity.Previously we reported that TFP5 peptide has neuroprotective effects in animal models of Alzheimer's disease.The neuroprotective effect of TFP5/TP5 peptide is also associated with marked reduction in neuroinflammation and apoptosis.

View Article: PubMed Central - PubMed

Affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

No MeSH data available.


Related in: MedlinePlus

TP5 protects from chronic MPTP-induced apoptosis. (A) Striatal tissue lysates from the brains of four groups of mice (as before) were prepared as Western blots to assay for the expression of key apoptotic marker molecules. A blot for cytochrome c shows a significant increase over controls after MPTP induction, which is completely reduced by TP5 treatment. (B) Quantification of A (ratio of cytochrome c to actin). (C, D) Expression levels of striatal cleaved caspase 3 and Bax (E, F) were also significantly increased in MPTP-group mice compared with controls. Here, too, treatment with TP5 significantly decreased the expression levels. Values are expressed as mean ± SEM (n = 3; ***p < 0.001; **p < 0.01, *p < 0.05).
© Copyright Policy - creative-commons
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4666141&req=5

Figure 7: TP5 protects from chronic MPTP-induced apoptosis. (A) Striatal tissue lysates from the brains of four groups of mice (as before) were prepared as Western blots to assay for the expression of key apoptotic marker molecules. A blot for cytochrome c shows a significant increase over controls after MPTP induction, which is completely reduced by TP5 treatment. (B) Quantification of A (ratio of cytochrome c to actin). (C, D) Expression levels of striatal cleaved caspase 3 and Bax (E, F) were also significantly increased in MPTP-group mice compared with controls. Here, too, treatment with TP5 significantly decreased the expression levels. Values are expressed as mean ± SEM (n = 3; ***p < 0.001; **p < 0.01, *p < 0.05).

Mentions: The loss of nigral dopaminergic neurons in PD results from extensive apoptosis marked by up-regulation of several apoptotic proteins (Levy et al., 2009). To determine whether TP5 inhibits neuronal apoptosis induced by MPTP, we subjected groups of mice to the standard protocol. At day 10, SN tissue was dissected, lysed, and prepared for Western blots with antibodies specific for cleaved caspase-3, Bax, and cytochrome c as an assay for apoptosis. The Western blot analysis showed that MPTP-evoked PD apoptotic phenotypes were significantly 1.5- to 2-fold greater than saline and SCP control injections (Figure 7, A and C). These changes, however, were significantly attenuated by TP5 treatment, in some cases almost to baseline levels (p < 0.05). Moreover, scrambled peptide–treated mice did not show any significant alterations. Our results are consistent with our hypothesis concerning the efficacy of TP5 treatment; prolonged treatment of TP5 markedly reduces the expression of apoptotic markers in PD mice.


Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson's disease.

Binukumar BK, Shukla V, Amin ND, Grant P, Bhaskar M, Skuntz S, Steiner J, Pant HC - Mol. Biol. Cell (2015)

TP5 protects from chronic MPTP-induced apoptosis. (A) Striatal tissue lysates from the brains of four groups of mice (as before) were prepared as Western blots to assay for the expression of key apoptotic marker molecules. A blot for cytochrome c shows a significant increase over controls after MPTP induction, which is completely reduced by TP5 treatment. (B) Quantification of A (ratio of cytochrome c to actin). (C, D) Expression levels of striatal cleaved caspase 3 and Bax (E, F) were also significantly increased in MPTP-group mice compared with controls. Here, too, treatment with TP5 significantly decreased the expression levels. Values are expressed as mean ± SEM (n = 3; ***p < 0.001; **p < 0.01, *p < 0.05).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4666141&req=5

Figure 7: TP5 protects from chronic MPTP-induced apoptosis. (A) Striatal tissue lysates from the brains of four groups of mice (as before) were prepared as Western blots to assay for the expression of key apoptotic marker molecules. A blot for cytochrome c shows a significant increase over controls after MPTP induction, which is completely reduced by TP5 treatment. (B) Quantification of A (ratio of cytochrome c to actin). (C, D) Expression levels of striatal cleaved caspase 3 and Bax (E, F) were also significantly increased in MPTP-group mice compared with controls. Here, too, treatment with TP5 significantly decreased the expression levels. Values are expressed as mean ± SEM (n = 3; ***p < 0.001; **p < 0.01, *p < 0.05).
Mentions: The loss of nigral dopaminergic neurons in PD results from extensive apoptosis marked by up-regulation of several apoptotic proteins (Levy et al., 2009). To determine whether TP5 inhibits neuronal apoptosis induced by MPTP, we subjected groups of mice to the standard protocol. At day 10, SN tissue was dissected, lysed, and prepared for Western blots with antibodies specific for cleaved caspase-3, Bax, and cytochrome c as an assay for apoptosis. The Western blot analysis showed that MPTP-evoked PD apoptotic phenotypes were significantly 1.5- to 2-fold greater than saline and SCP control injections (Figure 7, A and C). These changes, however, were significantly attenuated by TP5 treatment, in some cases almost to baseline levels (p < 0.05). Moreover, scrambled peptide–treated mice did not show any significant alterations. Our results are consistent with our hypothesis concerning the efficacy of TP5 treatment; prolonged treatment of TP5 markedly reduces the expression of apoptotic markers in PD mice.

Bottom Line: To date, strategies to specifically inhibit Cdk5 hyperactivity have not been successful without affecting normal Cdk5 activity.Previously we reported that TFP5 peptide has neuroprotective effects in animal models of Alzheimer's disease.The neuroprotective effect of TFP5/TP5 peptide is also associated with marked reduction in neuroinflammation and apoptosis.

View Article: PubMed Central - PubMed

Affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

No MeSH data available.


Related in: MedlinePlus