Scientists are making inroads because thousands of people with Parkinson’s and their family members have donated their brains to science, including to PDF-supported programs at Columbia University Medical Center and Rush University Medical Center.
PDF Grant Programs
Are you interested in furthering Parkinson's science? View PDF's open grant programs.
Prefoldin prevents aggregation of ?-synuclein.
PDF's targeted PubMed search provides you with access to journal articles from the last 90 days that may be pertinent to Parkinson's disease research.
Not what you're looking for? Do you need informational publications about Parkinson's targeted for people living with Parkinson's, caregivers and family members? Please browse PDF's educational materials and programs - which are all available electronically or in print. Order for yourself, a loved one or in bulk for your patients or support group.
Brain Res 2014 Jan; 1542:186-94
Authors: Mariko Takano, Erika Tashiro, Akira Kitamura, Hiroshi Maita, Sanae M M Iguchi-Ariga, Masataka Kinjo, Hiroyoshi Ariga
Protein aggregation is observed in various neurodegeneration diseases, including Parkinson's disease (PD). Alpha-synuclein, a causative gene product of familial PD, is a major component of large aggregates (inclusion bodies) in PD. Prefoldin, a molecular chaperone comprised of six subunits, PFD1~6, prevents misfolding of newly synthesized nascent polypeptides and also prevents aggregation of protein such as a pathogenic form of Huntingtin, a causative gene product of Huntington disease. In this study, we first found that aggregation of TagRFP-tagged wild-type ?-synuclein and its pathogenic mutants, but not that of GFP-tagged ?-synuclein, occurred in transfected Neuro-2a cells. The fluorescence of GFP is weakened under the condition of pH 4.5-5.0, and TagRFP is a stable red fluorescence protein under an acidic condition. Aggregated TagRFP-wild-type ?-synuclein and its pathogenic mutants in Neuro-2a cells were ubiquitinated and were colocalized with the prefoldin complex in the lysosome under this condition. Furthermore, knockdown of PFD2 and PFD5 disrupted prefoldin formation in ?-synuclein-expressing cells, resulting in accumulation of aggregates of wild-type and pathogenic ?-synuclein and in induction of cell death. The levels of aggregation and cell death in pathogenic ?-synuclein-transfected cells tended to be higher than those in wild-type ?-synuclein-transfected cells. These results suggest that prefoldin works as a protective factor in aggregated ?-synuclein-induced cell death.
PMID: 24511594 [PubMed - as supplied by publisher]