Intrinsically disordered proteins, such as tau or α-synuclein, have long been associated with a dysfunctional role in neurodegenerative diseases. In Alzheimer’s and Parkinson’s’ diseases, these proteins, sharing a...Intrinsically disordered proteins, such as tau or α-synuclein, have long been associated with a dysfunctional role in neurodegenerative diseases. In Alzheimer’s and Parkinson’s’ diseases, these proteins, sharing a common chemical-physical pattern with alternating hydrophobic and hydrophilic domains rich in prolines, abnormally aggregate in tangles in the brain leading to progressive loss of neurons. In this review, we present an overview linking the studies on the implication of the peptidyl-prolyl isomerase domain of immunophilins, and notably FKBP12, to a variety of neurodegenerative diseases, focusing on the molecular origin of such a role. The involvement of FKBP12 dysregulation in the aberrant aggregation of disordered proteins pinpoints this protein as a possible therapeutic target and, at the same time, as a predictive biomarker for early diagnosis in neurodegeneration, calling for the development of reliable, fast and cost-effective detection methods in body fluids for community-based screening campaigns.展开更多
AIMS: β-adrenergic augmentation of Ca2+ sparks and cardiac contractility has been functionally linked to phosphorylation-dependent dissociation of FK506 binding protein 12.
Rapamycin, similar to FKS06, can promote neural regeneration in vitro. We assumed that the mechanisms of action of rapamycin and FK506 in promoting peripheral nerve regeneration were similar. This study compared the e...Rapamycin, similar to FKS06, can promote neural regeneration in vitro. We assumed that the mechanisms of action of rapamycin and FK506 in promoting peripheral nerve regeneration were similar. This study compared the effects of different concentrations of raparnycin and FK506 on Sc hwann cells and investigated effects and mechanisms of rapamycin on improving peripheral nerve regeneration. Results demonstrated that the lowest rapamycin concentration （1.53 nmol/L） more significantly promoted Schwann cell migration than the highest FK506 concentration （100μmol/L）. Rapamycin promoted the secretion of nerve growth factors and upregulated growth-associated protein 43 expression in Schwann cells, but did not significantly affect Schwann cell proliferation. Therefore, rapamycin has potential application in peripheral nerve regeneration therapy.展开更多
哺乳类动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR），又称雷帕霉素相关蛋白（rapamycin associated protein，FRAP）或雷帕霉素与FK506结合蛋白12靶蛋白（rapamycin and FKBP12 target，RAFT1），是一类脯氨酸调控的丝...哺乳类动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR），又称雷帕霉素相关蛋白（rapamycin associated protein，FRAP）或雷帕霉素与FK506结合蛋白12靶蛋白（rapamycin and FKBP12 target，RAFT1），是一类脯氨酸调控的丝氨酸／苏氨酸（Ser／Thr）蛋白激酶，展开更多
文摘Intrinsically disordered proteins, such as tau or α-synuclein, have long been associated with a dysfunctional role in neurodegenerative diseases. In Alzheimer’s and Parkinson’s’ diseases, these proteins, sharing a common chemical-physical pattern with alternating hydrophobic and hydrophilic domains rich in prolines, abnormally aggregate in tangles in the brain leading to progressive loss of neurons. In this review, we present an overview linking the studies on the implication of the peptidyl-prolyl isomerase domain of immunophilins, and notably FKBP12, to a variety of neurodegenerative diseases, focusing on the molecular origin of such a role. The involvement of FKBP12 dysregulation in the aberrant aggregation of disordered proteins pinpoints this protein as a possible therapeutic target and, at the same time, as a predictive biomarker for early diagnosis in neurodegeneration, calling for the development of reliable, fast and cost-effective detection methods in body fluids for community-based screening campaigns.
文摘AIMS: β-adrenergic augmentation of Ca2+ sparks and cardiac contractility has been functionally linked to phosphorylation-dependent dissociation of FK506 binding protein 12.
基金supported by the Major State Basic Research Development Program of China(973 Program),No.2011CB606205the National Natural Science Foundation of China,No.51172171 and 51103112+2 种基金the Key Project of Chinese Ministry of Education,No.313041the Natural Science Foundation of Hubei Province,No.2013CFB354the Fundamental Research Funds for the Central Universities,No.WUT:2013-IV-099
文摘Rapamycin, similar to FKS06, can promote neural regeneration in vitro. We assumed that the mechanisms of action of rapamycin and FK506 in promoting peripheral nerve regeneration were similar. This study compared the effects of different concentrations of raparnycin and FK506 on Sc hwann cells and investigated effects and mechanisms of rapamycin on improving peripheral nerve regeneration. Results demonstrated that the lowest rapamycin concentration （1.53 nmol/L） more significantly promoted Schwann cell migration than the highest FK506 concentration （100μmol/L）. Rapamycin promoted the secretion of nerve growth factors and upregulated growth-associated protein 43 expression in Schwann cells, but did not significantly affect Schwann cell proliferation. Therefore, rapamycin has potential application in peripheral nerve regeneration therapy.
文摘哺乳类动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR），又称雷帕霉素相关蛋白（rapamycin associated protein，FRAP）或雷帕霉素与FK506结合蛋白12靶蛋白（rapamycin and FKBP12 target，RAFT1），是一类脯氨酸调控的丝氨酸／苏氨酸（Ser／Thr）蛋白激酶，
