Prolyl oligopeptidase and dipeptidyl peptidase II/dipeptidyl peptidase IV ratio in the cerebrospinal fluid in Parkinson’s disease: historical overview and future prospects

Nagatsu, Toshiharu

doi:10.1007/s00702-016-1604-8

Cited by 13 publications

(8 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many other candidate markers have been reported ( Table 1 ) [ 6 , 9 , 18 , 25 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 61 ]; however, these candidates also include preliminary ones with small sample data. These markers require verification and interpretation of the background.…”

Section: Resultsmentioning

confidence: 99%

Cerebrospinal Fluid Biomarkers in Parkinson’s Disease: A Critical Overview of the Literature and Meta-Analyses

et al. 2020

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a common neurodegenerative disorder; however, well-established biochemical markers have not yet been identified. This review article covers several candidate cerebrospinal fluid (CSF) biomarkers for PD based on the recent literature and meta-analysis data. The decrease of α-synuclein in PD is supported by meta-analyses with modest reproducibility, and a decrease of amyloid β42 is seen as a prognostic marker for cognitive decline. Tau, phosphorylated tau (p-tau), and neurofilament light chains have been used to discriminate PD from other neurodegenerative disorders. This article also describes more hopeful biochemical markers, such as neurotransmitters, oxidative stress markers, and other candidate biomarkers.

show abstract

Section: Resultsmentioning

confidence: 99%

Cerebrospinal Fluid Biomarkers in Parkinson’s Disease: A Critical Overview of the Literature and Meta-Analyses

et al. 2020

View full text Add to dashboard Cite

show abstract

“…POP is a prototypic proline specific endopeptidase with high cytosolic expression levels in several tissues, e.g. neurons and immune cells ( Mannisto and Garcia-Horsman, 2017 ; Nagatsu, 2017 ). From a molecular point of view, the enzyme has high substrate specificity for motifs with only trans -configured proline residues in the P1 position and only modest affinities for alanine and cysteine residues ( Bär et al, 2006 ).…”

Section: Introductionmentioning

confidence: 99%

“…Small peptide substrates, usually no greater than ∼3 kDa have access to the protease binding pocket ( Fülöp et al, 1998 ; Hellinger et al, 2015a ). POP has an important role in peptide hormone homeostasis ( Lambeir, 2011 ; Nagatsu, 2017 ) and many peptide hormones e.g. Arg-vasopressin, substance P, oxytocin, bradykinin and neurotensin have been identified as substrates of POP ( López et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

“…More recently, POP has been investigated as target for inflammation and neurodegenerative disorders, such as multiple sclerosis ( Tenorio-Laranga et al, 2013 ) and Parkinson’s disease ( Dokleja et al, 2014 ; Mannisto and Garcia-Horsman, 2017 ). Despite many research studies the evidence for the pathological role of POP in these diseases is still unclear since disease-relevant brain signaling pathways modulated by POP have not been identified to date ( Mannisto and Garcia-Horsman, 2017 ; Nagatsu, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cyclotides Isolated From Violet Plants of Cameroon Are Inhibitors of Human Prolyl Oligopeptidase

et al. 2021

View full text Add to dashboard Cite

Traditional medicine and the use of herbal remedies are well established in the African health care system. For instance, Violaceae plants are used for antimicrobial or anti-inflammatory applications in folk medicine. This study describes the phytochemical analysis and bioactivity screening of four species of the violet tribe Allexis found in Cameroon. Allexis cauliflora, Allexis obanensis, Allexis batangae and Allexis zygomorpha were evaluated for the expression of circular peptides (cyclotides) by mass spectrometry. The unique cyclic cystine-rich motif was identified in several peptides of all four species. Knowing that members of this peptide family are protease inhibitors, the plant extracts were evaluated for the inhibition of human prolyl oligopeptidase (POP). Since all four species inhibited POP activity, a bioactivity-guided fractionation approach was performed to isolate peptide inhibitors. These novel cyclotides, alca 1 and alca 2 exhibited IC50 values of 8.5 and 4.4 µM, respectively. To obtain their amino acid sequence information, combinatorial enzymatic proteolysis was performed. The proteolytic fragments were evaluated in MS/MS fragmentation experiments and the full-length amino acid sequences were obtained by de novo annotation of fragment ions. In summary, this study identified inhibitors of the human protease POP, which is a drug target for inflammatory or neurodegenerative disorders.

show abstract

“…Prolyl oligopeptidase (POP, EC 3.4.21.26) is a large cytosolic serine peptidase that is widely distributed in the CNS, including in the hypothalamus, striatum, hippocampus, cortex, and amygdala. POP specifically cleaves peptide bonds at the carboxylic end of proline residues in proline–containing endogenous peptides [reviewed in ( Garcia-Horsman et al, 2007 ; Mannisto et al, 2007 ; Peltonen et al, 2011 ; Nagatsu, 2017 )]. For example, POP hydrolyses thyroliberin, vasopressin, neurotensin, substance P, angiotensin, bradykinin, oxytocin, and other regulatory neuropeptides ( Garcia-Horsman et al, 2007 ; Svarcbahs et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Effect of Novel Cyanopyrrolidine-Based Prolyl Oligopeptidase Inhibitors in Rat Models of Amnesia

et al. 2021

View full text Add to dashboard Cite

Prolyl oligopeptidase (POP) is a large cytosolic serine peptidase that is altered in patients with Alzheimer’s disease, Parkinsonian syndrome, muscular dystrophies, and other denervating diseases. Thus, POP may represent a relevant therapeutic target for treatment of neuropsychiatric disorders and neurodegenerative diseases. Here, we report the characterization of five novel cyanopyrrolidine-based compounds (BocTrpPrdN, BocGlyPrdN, CbzMetPrdN, CbzGlnPrdN, and CbzAlaPrdN) and show that they are potent inhibitors of POP and are predicted to penetrate the blood-brain barrier (BBB). Indeed, we show that CbzMetPrdN penetrates the rat BBB and effectively inhibits POP in the brain when administered intraperitoneally. Furthermore, molecular modeling confirmed these compounds likely inhibit POP via interaction with the POP catalytic site. We evaluated protective effects of the cyanopyrrolidine-based POP inhibitors using scopolamine- and maximal electroshock-induced models of amnesia in rats and showed that BocTrpPrdN, BocGlyPrdN, CbzMetPrdN, and CbzGlnPrdN significantly prolonged conditioned passive avoidance reflex (CPAR) retention time when administered intraperitoneally (1 and 2 mg/kg) before evaluation in both models of amnesia, although CbzAlaPrdN was not effective in scopolamine-induced amnesia. Our data support previous reports on the antiamnesic effects of prolinal-based POP inhibitors and indicate an important role of POP in the regulation of learning and memory processes in the CNS.

show abstract

Prolyl oligopeptidase and dipeptidyl peptidase II/dipeptidyl peptidase IV ratio in the cerebrospinal fluid in Parkinson’s disease: historical overview and future prospects

Cited by 13 publications

References 47 publications

Cerebrospinal Fluid Biomarkers in Parkinson’s Disease: A Critical Overview of the Literature and Meta-Analyses

Cerebrospinal Fluid Biomarkers in Parkinson’s Disease: A Critical Overview of the Literature and Meta-Analyses

Cyclotides Isolated From Violet Plants of Cameroon Are Inhibitors of Human Prolyl Oligopeptidase

Therapeutic Effect of Novel Cyanopyrrolidine-Based Prolyl Oligopeptidase Inhibitors in Rat Models of Amnesia

Contact Info

Product

Resources

About