Vaš brskalnik ne omogoča JavaScript!
JavaScript je nujen za pravilno delovanje teh spletnih strani. Omogočite JavaScript ali pa uporabite sodobnejši brskalnik.
Nacionalni portal odprte znanosti
Odprta znanost
DiKUL
slv
|
eng
Iskanje
Brskanje
Novo v RUL
Kaj je RUL
V številkah
Pomoč
Prijava
Cysteine peptidase cathepsin X as a therapeutic target for simultaneous TLR3/4-mediated microglia activation
ID
Pišlar, Anja
(
Avtor
),
ID
Božić Nedeljković, Biljana
(
Avtor
),
ID
Perić, Mina
(
Avtor
),
ID
Jakoš, Tanja
(
Avtor
),
ID
Zidar, Nace
(
Avtor
),
ID
Kos, Janko
(
Avtor
)
PDF - Predstavitvena datoteka,
prenos
(1,63 MB)
MD5: B6A1F14256F78603B69F6FCE1A202178
URL - Izvorni URL, za dostop obiščite
https://link.springer.com/article/10.1007/s12035-021-02694-2
Galerija slik
Izvleček
Microglia are resident macrophages in the central nervous system that are involved in immune responses driven by toll-like receptors (TLRs). Microglia-mediated inflammation can lead to central nervous system disorders, and more than one TLR might be involved in these pathological processes. The cysteine peptidase cathepsin X has been recognized as a pathogenic factor for inflammation-induced neurodegeneration. Here, we hypothesized that simultaneous TLR3 and TLR4 activation induces synergized microglia responses and that these phenotype changes affect cathepsin X expression and activity. Murine microglia BV2 cells and primary murine microglia were exposed to the TLR3 ligand polyinosinic-polycytidylic acid (poly(I:C)) and the TLR4 ligand lipopolysaccharide (LPS), individually and simultaneously. TLR3 and TLR4 co-activation resulted in increased inflammatory responses compared to individual TLR activation, where poly(I:C) and LPS induced distinct patterns of proinflammatory factors together with different patterns of cathepsin X expression and activity. TLR co-activation decreased intracellular cathepsin X activity and increased cathepsin X localization at the plasma membrane with concomitant increased extracellular cathepsin X protein levels and activity. Inhibition of cathepsin X in BV2 cells by AMS36, cathepsin X inhibitor, significantly reduced the poly(I:C)- and LPS-induced production of proinflammatory cytokines as well as apoptosis. Additionally, inhibiting the TLR3 and TLR4 common signaling pathway, PI3K, with LY294002 reduced the inflammatory responses of the poly(I:C)- and LPS-activated microglia and recovered cathepsin X activity. We here provide evidence that microglial cathepsin X strengthens microglia activation and leads to subsequent inflammation-induced neurodegeneration. As such, cathepsin X represents a therapeutic target for treating neurodegenerative diseases related to excess inflammation.
Jezik:
Angleški jezik
Ključne besede:
microglia
,
toll-like receptors
,
cathepsin X
,
proinfammatory mediators
,
neuroinfammation
,
neuroprotection
Vrsta gradiva:
Članek v reviji
Tipologija:
1.01 - Izvirni znanstveni članek
Organizacija:
FFA - Fakulteta za farmacijo
Status publikacije:
Objavljeno
Različica publikacije:
Objavljena publikacija
Leto izida:
2022
Št. strani:
Str. 2258–2276
Številčenje:
Vol. 59, iss. 4
PID:
20.500.12556/RUL-145265
UDK:
616-097:616.8
ISSN pri članku:
0893-7648
DOI:
10.1007/s12035-021-02694-2
COBISS.SI-ID:
95406083
Datum objave v RUL:
14.04.2023
Število ogledov:
657
Število prenosov:
76
Metapodatki:
Citiraj gradivo
Navadno besedilo
BibTeX
EndNote XML
EndNote/Refer
RIS
ABNT
ACM Ref
AMA
APA
Chicago 17th Author-Date
Harvard
IEEE
ISO 690
MLA
Vancouver
:
Kopiraj citat
Objavi na:
Gradivo je del revije
Naslov:
Molecular neurobiology
Skrajšan naslov:
Mol. neurobiol.
Založnik:
Springer Nature
ISSN:
0893-7648
COBISS.SI-ID:
25975552
Licence
Licenca:
CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:
http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:
To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Sekundarni jezik
Jezik:
Slovenski jezik
Ključne besede:
mikroglija
,
receptorji TLR
,
katepsin X
,
protivnetni mediatorji
,
nevrovnetje
,
nevroprotekcija
,
motnje živčnega sistema
,
imunski odziv
Projekti
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
P4-0127
Naslov:
Farmacevtska biotehnologija: znanost za zdravje
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
J4-4123
Naslov:
Inhibitorji cisteinskih karboksipeptidaz kot regulatorji avtoimunskih in nevrodegenerativnih procesov
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
J3-9267
Naslov:
Zaviranje aktivnosti katepsina X kot nov pristop za zdravljenje Parkinsonove bolezni
Financer:
Drugi - Drug financer ali več financerjev
Program financ.:
Republic of Slovenia, Ministry of Education, Science and Sport
Številka projekta:
451–03-68/2020–14/200178
Financer:
Drugi - Drug financer ali več financerjev
Program financ.:
Republic of Slovenia, Bilateral Projects
Financer:
Drugi - Drug financer ali več financerjev
Program financ.:
Republic of Serbia, Bilateral Projects
Podobna dela
Podobna dela v RUL:
Podobna dela v drugih slovenskih zbirkah:
Nazaj