Multidisciplinary approaches to coping with neurodegenerative disorders amid COVID-19 pandemic

Table 2. Natural compounds enhancing the clearance of protein aggregates

Compound	Dose	Experimental disease model	Specific target pathway	Research outcomes and molecular changes	Ref.
Phenolic compounds
Oleocanthal	10 mg/kg	C57BL/6 wild-type male mice (¹²⁵I-Aβ_40,30 nM)	Aggregates clearance	↑¹²⁵I-Aβ₄₀ degradation ↑P-gp and LRP1 expression	[57]
Oleuropein aglycone	50 mg/kg of diet	transgenic TgCRND8 mice	Autophagy	Anti-inflammatory and antioxidant effects ↑Neuronal autophagy	[58]
Kaempferol	30 mM	SH-SY5Y cells	Autophagy	↑Neuronal autophagy ↑LC3-II	[59]
Non-phenolic compounds
Berberine	40 mg/kg BW of mice, 50 μM in HEK293 cells	Transgenic N171-82Q mice, Htt-transfected HEK293 cells	Autophagy	Alleviates motor dysfunction ↓P62 ↑LC3B-II	[92]
Sulforaphane	0.5 mg/kg SFN 10uM in HeLa and HEK293 cells	HeLa and HEK293 cells transfected with GFP-tagged Htt-exon1 containing 74Q GFPu transgenic UPS function model mouse	UPS-mediated proteolysis	↑chymotrypsin-like, caspase-like, and trypsin-like activities ↑LC3-I and LC3-II protein levels	[61]
Geldanamycin	500nM	Drosophila – N-terminal HTT fragment Q128 R6/2 mouse – HTT exon 1 Q150 COS1 cells – express N-terminal HTT Q51	Molecular chaperone system	↑Hsp70, Hsp40, and Hsp90 expression	[62]
Celastrol	1.6 uM	HeLa, PC12 cells, HSF1+/+ and HSF1-/- mouse embryo fibroblast (MEF) cells	Upregulate hsp gene expression	↑Hsp70 ↓Q57-YFP-aggregates	[63]

P-gp, P-glycoprotein; LRP1, LDL lipoprotein receptor related protein-1; LC3-I, Microtubule-associated protein light chain-3-I; LC3-II, Light chain-3-II; Hsp70, 70-kDa heat shock proteins; Hsp90, Heat shock protein 90.