Healthspan improvement and anti-aggregation effects induced by a marine-derived structural proteasome activator

Neuron-specific proteasome activation exerts cell non-autonomous protection against amyloid-beta (Aβ) proteotoxicity in Caenorhabditis elegans

“…This suggests that proteasome activation may promote the degradation of Aβ species before they become highly aggregated and thus inaccessible and inhibitory to the proteasome [ 57 , 58 ]. In our previous work, proteasome activation through genetic means (systemic pbs-5 overexpression) [ 10 ] or through natural compounds with proteasome-activating properties [ 59 , 60 ], had elicited similar results. Likewise, in a very recent work, genetic and pharmacological proteasome augmentation also resulted in enhanced clearance of APP in flies, cultured cells and mice [ 8 ].…”

Beneficial Effects of Sideritis clandestina Extracts and Sideridiol against Amyloid β Toxicity

“…The accelerated defecation rate is associated with enhanced fitness of the animals, which permits faster detoxification [ 72 ]. Additionally, enhanced pharyngeal pumping has been linked to longevity [ 71 , 73 ], and various compounds positively affecting the lifespan of the animals have been shown to accelerate pharyngeal pumping rate [ 42 , 43 , 85 ]. Therefore, those alterations can be considered as beneficial ones.…”

“…N2 animals laid eggs for 20–30 min on NGM plates containing either the tested extract or compound or the diluent (DMSO or H 2 O). The following phenotypic characteristics were monitored as previously described [ 42 , 43 ].…”

Interactions Between the Ubiquitin–Proteasome System, Nrf2, and the Cannabinoidome as Protective Strategies to Combat Neurodegeneration: Review on Experimental Evidence

“…18α-GA 18α-glycyrrhetinic acid; Akt protein kinase B; DBTO (1R,3E,6R,7Z,11S,12S)-dolabella-3,7,18-trien-6,17-olide; GABA B γ-aminobutyric acid receptor B; LMP7 20S proteasome subunit β 8; MPP + 1-methyl-4-phenylpyridinium; mTOR mechanistic target of rapamycin; PAP1 proteasome-activating peptide 1; PA28γ proteasome activator 28γ; PKA protein kinase A; p60S6K p60S6-kinase; PSMD1 26S proteasome regulatory subunit N2 Disease Experimental approach Main results of UPS potentiation Reference AD 5xFAD mice (transgenic AD mice model) were treated with a combination of 18α-GA and omega-3 fatty acids (proteasome activators) Proteasome activator exposure improved proteasome activity while reducing Aβ coverage within both the hippocampus and cortex of 5xFAD mice. In vivo, this treatment also enhanced vertical and locomotor activity of the rodents (Djordjevic et al 2021 ) SH-SY5Y cells were exposed to Aβ toxicity and treated with DBTO (proteasome activator) DBTO treatment successfully enhanced proteasome activity in SH-SY5Y cultures, consequently improving cell survival to Aβ cytotoxic effects (Vasilopoulou et al 2022 ) 3x-Tg transgenic mice were fed for 10 months with a diet supplemented with resveratrol Resveratrol induced an increase in proteasome activity and protein levels of 20S core particles, which was accompanied with a reduction of ubiquitinated proteins, phosphorylated Tau, and Aβ oligomers (Corpas et al 2019 ) SH-SY5Y cell cultures were transfected to express truncated forms of Tau protein. Afterwards, it was evaluated the neuroprotective potential of geldanamycin in the cultures The expression of the truncated form of Tau protein led to the generation of intracellular aggregates and the inhibition of the activity of proteasome.…”