Proteasome activation plays role in 18α-glycyrrhetinic acid protectiveeffect in 5XFAD animal model of Alzheimer’s disease
2017
Autori:
Mladenović, AleksandraJović, Milena
Lončarević-Vasiljković, Nataša
Athanasopoulou, Sofia
Gonos, Efstathios S
Kanazir, Selma
Ostala autorstva
Kanazir, SelmaBjelobaba, Ivana
Tip dokumenta:
Konferencijski prilog (Objavljena verzija)
,
© 2017 by the Serbian Neuroscience Society
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
Introduction. Aging represents the most important risk factor for Alzheimer’s
disease (AD), the most common neurodegenerative disorders worldwide. One of
the hallmarks of AD is the accumulation of plaques composed of aggregated
amyloid-β peptides (Aβ) which are formed by sequential proteolytic processing
of the amyloid-precursor protein (APP).It is well known that different factors
can influence amyloidogenic pathway and/or clearance of already formed Aβ.
Growing evidence suggest that ubiquitin proteasomal system represents an
important factor in AD development and a potential target for the management
of disease. Recently it has been shown that several natural compounds,
including 18α-glycyrrhetinic acid (18α-GA) protects from protein aggregation related pathology in AD model system. Methods. In order to investigate the
protective effect of 18α-GA, we used 5xFAD transgenic mouse AD model,
characterized by early amyloid deposition and intra-neuronal Aβ42 aggregation.
Both female and male mice were exposed to 18α-GA treatment for one month,
started at 2-months of age. This is considered as an early phase of AD pathology,
known to be suitable for therapeutics application. In the cortex and
hippocampus CT-L, T-L, and PGPH proteasome activities were assayed by
hydrolysis of Suc-LLVY-AMC, Boc-LRR-AMC, and Z-LLE-AMC fluorogenic
peptides. The number and size of amyloid plaques were determined in these
structures. Results. This study revealed that 18α-GA treatment influence
neuritic dystrophy, increase proteasome activity, decrease Aβ content and
number of amyloid plaques in 5xFAD mice. Conclusion. These preliminary
intriguing data open up new directions using natural compounds for the most
efficient treatment of neurodegenerative disorders.
Ključne reči:
Aging; Alzheimer's diseaseFinansiranje / projekti:
- COST Action CA15214 STSM grant (№ CA15214-300117-082476)
- Plastičnost mozga tokom starenja: uticaj dijetalne restrikcije i anestezije (RS-MESTD-Basic Research (BR or ON)-173056)
U:
- Kanazir S, Bjelobaba I, editors. Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia. Belgrade: Serbian Neuroscience Society; 2017. p. 109.