ArticleThe Journal of biological chemistry2011
Comparative analysis of different peptidyl-prolyl isomerases reveals FK506-binding protein 12 as the most potent enhancer of alpha-synuclein aggregation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- The Role of FKBPs in Complex Disorders: Neuropsychiatric Diseases, Cancer, and Type 2 Diabetes Mellitus.Cells · 2024Review
- Conserved region of human TDP-43 is structurally similar to membrane binding protein FARP1 and protein chaperons BAG6 and CYP33.microPublication biology · 2024Article
- Furanoditerpenes fromACS chemical neuroscience · 2022Article
- FKBP52 in Neuronal Signaling and Neurodegenerative Diseases: A Microtubule Story.International journal of molecular sciences · 2022Review
- Humanized Mice for Infectious and Neurodegenerative disorders.Retrovirology · 2021Review
- The Molecular Basis of the Interaction of Cyclophilin A with α-Synuclein.Angewandte Chemie (International ed. in English) · 2020Article
- Blocking the FKBP12 induced dendrimeric burst in aberrant aggregation of α-synuclein by using the ElteN378 synthetic inhibitor.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Identification of a Specific Gene Module for Predicting Prognosis in Glioblastoma Patients.Frontiers in oncology · 2019Article
- S-nitrosylation of UCHL1 induces its structural instability and promotes α-synuclein aggregation.Scientific reports · 2017Article
- The Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in Alzheimer's Disease.Molecular neurobiology · 2016Review
- Noninvasive bioluminescence imaging of α-synuclein oligomerization in mouse brain using split firefly luciferase reporters.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- In vitro screen of prion disease susceptibility genes using the scrapie cell assay.Human molecular genetics · 2014Article
- FKBP12 regulates the localization and processing of amyloid precursor protein in human cell lines.Journal of biosciences · 2014Article
- In vitro phosphorylation does not influence the aggregation kinetics of WT α-synuclein in contrast to its phosphorylation mutants.International journal of molecular sciences · 2014Article
- A prolyl oligopeptidase inhibitor, KYP-2047, reduces α-synuclein protein levels and aggregates in cellular and animal models of Parkinson's disease.British journal of pharmacology · 2012Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
FK506-binding proteins (FKBPs) are members of the immunophilins, enzymes that assist protein folding with their peptidyl-prolyl isomerase (PPIase) activity. Some non-immunosuppressive inhibitors of these enzymes have neuroregenerative and neuroprotective properties with an unknown mechanism of action. We have previously shown that FKBPs accelerate the aggregation of α-synuclein (α-SYN) in vitro and in a neuronal cell culture model for synucleinopathy. In this study we investigated whether acceleration of α-SYN aggregation is specific for the FKBP or even the PPIase family. Therefore, we studied the effect of several physiologically relevant PPIases, namely FKBP12, FKBP38, FKBP52, FKBP65, Pin1, and cyclophilin A, on α-SYN aggregation in vitro and in neuronal cell culture. Among all PPIases tested in vitro, FKBP12 accelerated α-SYN aggregation the most. Furthermore, only FKBP12 accelerated α-SYN fibril formation at subnanomolar concentrations, pointing toward an enzymatic effect. Although stable overexpression of various FKBPs enhanced the aggregation of α-SYN and cell death in cell culture, they were less potent than FKBP12. When FKBP38, FKBP52, and FKBP65 were overexpressed in a stable FKBP12 knockdown cell line, they could not fully restore the number of α-SYN inclusion-positive cells. Both in vitro and cell culture data provide strong evidence that FKBP12 is the most important PPIase modulating α-SYN aggregation and validate the protein as an interesting drug target for Parkinson disease.
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