title: Prolyl oligopeptidase and dipeptidyl peptidase II/dipeptidyl peptidase IV ratio in the cerebrospinal fluid in Parkinson's disease: historical overview and future prospects.
abstract: Prolyl oligopeptidase (also named prolyl endopeptidase; PREP) hydrolyzes the Pro-Xaa bonds of biologically active oligopeptides on their carboxyl side. In 1987, we detected PREP activity in human cerebrospinal fluid (CSF) using highly sensitive liquid chromatography-fluorometry with succinyl-Gly-Pro-4-methyl-coumarin amide as a new synthetic substrate, and found a marked decrease in its activity in the cerebrospinal fluid (CSF) from patients with Parkinson's disease (PD) as compared with its level in control patients without neurological diseases. In 2013, Hannula et al. found co-localization of PREP with α-synuclein in the postmortem PD brain. Several recent studies also suggest that the level of PREP in the brain of PD patients may be related to dopamine (DA) cell death via promotion of α-synuclein oligomerization and that inhibitors of PREP may play a neuroprotective role in PD. Although the relationship between another family of prolyl oligopeptidase enzymes, dipeptidyl peptidase II (DPP II) and dipeptidyl peptidase IV (DPP IV), and α-synuclein in the PD brain is not yet clear, we found that the DPP II activity/DPP IV activity ratio in the CSF was significantly increased in PD patients. This review discusses the possibility of PREP as well as the DPP II/DPP IV ratio in the CSF as potential biomarkers of PD.
authors: Department of Pharmacology, School of Medicine, Fujita Health University, Toyoake, Aichi, 470-1192, Japan. tnagatsu@fujita-hu.ac.jp.|Department of Brain Functions, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, 464-8601, Japan. tnagatsu@fujita-hu.ac.jp.
authors: Toshiharu
authors: T
authors: Nagatsu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D018819:Dipeptidyl Peptidase 4 / Q000134:cerebrospinal fluid*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000134:cerebrospinal fluid*; D006801:Humans; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000201:enzymology*; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100151:dipeptidyl peptidase II; D018819:Dipeptidyl Peptidase 4; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases
keywords: Biomarkers; Cerebrospinal fluid; Dipeptidyl peptidase II/dipeptidyl peptidase IV ratio; Parkinson’s disease; Prolyl oligopeptidase