Effective Reduction of Tau Amyloid Aggregates in the Presence of Cyclophilin from
Alzheimer's disease (AD)
amyloid aggregation
cell cytoplasm
cytoplasmic proteins
microtubules
plant cyclophilin (P-Cyp)
Journal
Current protein & peptide science
ISSN: 1875-5550
Titre abrégé: Curr Protein Pept Sci
Pays: United Arab Emirates
ID NLM: 100960529
Informations de publication
Date de publication:
2023
2023
Historique:
received:
22
11
2022
revised:
10
04
2023
accepted:
17
04
2023
medline:
29
8
2023
pubmed:
1
6
2023
entrez:
1
6
2023
Statut:
ppublish
Résumé
A hallmark pathology of Alzheimer's disease (AD) is the construction of neurofibrillary tangles, which are made of hyperphosphorylated Tau. The cis-proline isomer of the pThr/Ser-Pro sequence has been suggested to act as an aggregation precursor according to the 'Cistauosis' hypothesis; however, this aggregation scheme is not yet completely approved. Various peptidyl-prolyl isomerases (PPIases) may specifically isomerize cis/trans-proline bonds and restitute Tau's ability to attach microtubules and may control Tau amyloid aggregation in AD. In this study, we provided experimental evidence for indicating the effects of the plant Cyclophilin (P-Cyp) from Our findings disclosed that the rate/extent of amyloid formation in the Tau sample which is incubated with P-Cyp decreased and these observations do not seem to be due to the macromolecular crowding effect. Also, as proven that 80% of the prolines in the unfolded protein are in the trans conformation, urea-induced unfolding analyses confirmed this conclusion and showed that the aggregation rate/extent of urea-treated Tau samples decreased compared with those of the native protein. Also, XRD analysis indicated the reduction of scattering intensities and beta structures of amyloid fibrils in the presence of P-Cyp. Therefore, the ability of P-Cyp to suppress Tau aggregation probably depends on cis to trans isomerization of proline peptide bonds (X-Pro) and decreasing cis isomers The findings of the current study may inspire possible protective/detrimental effects of various types of cyclophilins on AD onset/progression through direct regulation of intracellular Tau molecules and provides evidence that a protein from a plant source is able to enter the cell cytoplasm and may affect the behavior of cytoplasmic proteins.
Sections du résumé
BACKGROUND
BACKGROUND
A hallmark pathology of Alzheimer's disease (AD) is the construction of neurofibrillary tangles, which are made of hyperphosphorylated Tau. The cis-proline isomer of the pThr/Ser-Pro sequence has been suggested to act as an aggregation precursor according to the 'Cistauosis' hypothesis; however, this aggregation scheme is not yet completely approved. Various peptidyl-prolyl isomerases (PPIases) may specifically isomerize cis/trans-proline bonds and restitute Tau's ability to attach microtubules and may control Tau amyloid aggregation in AD.
METHODS
METHODS
In this study, we provided experimental evidence for indicating the effects of the plant Cyclophilin (P-Cyp) from
RESULTS
RESULTS
Our findings disclosed that the rate/extent of amyloid formation in the Tau sample which is incubated with P-Cyp decreased and these observations do not seem to be due to the macromolecular crowding effect. Also, as proven that 80% of the prolines in the unfolded protein are in the trans conformation, urea-induced unfolding analyses confirmed this conclusion and showed that the aggregation rate/extent of urea-treated Tau samples decreased compared with those of the native protein. Also, XRD analysis indicated the reduction of scattering intensities and beta structures of amyloid fibrils in the presence of P-Cyp. Therefore, the ability of P-Cyp to suppress Tau aggregation probably depends on cis to trans isomerization of proline peptide bonds (X-Pro) and decreasing cis isomers
CONCLUSION
CONCLUSIONS
The findings of the current study may inspire possible protective/detrimental effects of various types of cyclophilins on AD onset/progression through direct regulation of intracellular Tau molecules and provides evidence that a protein from a plant source is able to enter the cell cytoplasm and may affect the behavior of cytoplasmic proteins.
Identifiants
pubmed: 37259218
pii: CPPS-EPUB-132164
doi: 10.2174/1389203724666230530143704
doi:
Substances chimiques
Cyclophilins
EC 5.2.1.-
Amyloid
0
Allergens
0
tau Proteins
0
Proline
9DLQ4CIU6V
Urea
8W8T17847W
Amyloid beta-Peptides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
518-532Subventions
Organisme : Kermanshah University of Medical Sciences
ID : 96216,96216
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.