Table 1.
Effects of HTyr or OLE on age-associated neurodegenerative diseases.
| Disease | System | Action | Reference |
|---|---|---|---|
| Alzheimer’s disease | SH-SY5Y APP695 cells | HTyr enhances ATP production; ligstroside enhances mitochondrial respiration | [124] |
| In vitro (biochemistry) | HTyr and OLE inhibit fibrillization of Tau protein | [127] | |
| SH-SY5Y cells | HTyr prevents β-amyloid aggregation (i.e., Aβ1–42 oligomer formation) | [121] | |
| SH-SY5Y cells | OLE prevents β-amyloid aggregation/cytotoxicity (i.e., Aβ1–42 oligomer formation) | [128] | |
| i.c.v. injection of Aβ oligomers | HTyr restores spatial and working memory and prevents apoptosis | [129] | |
| TgCRND8 mice | HTyr prevents amyloid-β deposition, with cognitive benefit; decrease of TNF-α | [130] | |
| TgCRND8 mice (12-m-old) | OLE prevents amyloid-β deposition, in cortex and hippocampus; restores LTP | [131] | |
| TgCRND8 mice (4-m-old) | OLE (12.5 mg/Kg) reduces Aβ plaque and restores cognitive performance | [132] | |
| C. elegans | OLE reduces amyloid-β aggregation and increases lifespan | [133] | |
| β-cells | OLE through HTyr prevents amylin aggregation | [134] | |
| In vitro and SH-SY5Y cells | OLE prevents the deposition of α-synuclein | [135] | |
| PC12 cells | HTyr prevents the abnormal assembly of α-synuclein and increases SIRT2 | [136] | |
| APP/Ps1 mice | HTyr reduces mitochondrial protein oxidation and brain inflammation | [137] | |
| APP/Ps1 mice | HTyr improves spatial memory and reduces hippocampus apoptosis Erβ-dependently | [138] | |
| 7PA2 cell Aβ accumulation model | HTyr restores mitochondrial energetic deficit | [139] | |
| SH-SY5Y cells | HTyr and OLE, after exposure to Aβ, activate autophagy preventing ROS | [140] | |
| N2a cells | HTyr counteracts NF-kB activation and cell death induced by Aβ25–35 treatment | [141] | |
| Astrocytes (C6 cells) | HTyr is neuroprotective by restoring insulin signaling damaged by Aβ25–35 treatment | [142] | |
| Parkinson’s disease | 6-OHDA in SH-SY5Y cells | HTyr butyrate inhibits ROS-dependent apoptosis through Nrf2/HO-1 activation | [143] |
| 6-OHDA in PC12 cells | HTyr inhibits apoptosis through increase of nuclear Nrf2 protein levels | [144] | |
| 6-OHDA in PC12 cells | OLE inhibits apoptosis reducing mitochondrial ROS production and favoring autophagy | [145] | |
| DA or 6-OHDA in SH-SY5Y cells | HTyr prevents dopamine toxicity by inducing phase II enzymes (GST, HO-1, NQO1) | [146] | |
| MAO inhibitors in PC12 cells | HTyr inhibits the production of toxic dopamine metabolite DOPAL | [147] | |
| MPP+ injection in mice striatum | HTyr inhibits MAO activity in striatum | [148] | |
| MPP+ injection in mice striatum | HTyr, HTyr acetate, nitro-HTyr reduce ipsilateral turns, increase GSH/GSSG ratio | [149] | |
| Rotenone injection in mice | OLE is anti-apoptotic by reducing mitochondrial ROS and α-synuclein aggregation | [150] | |
| SH-SY5Y cells | HTyr stabilizes specific areas of α-synuclein structure, preventing fibrillation | [151] | |
| Escherichia coli BL21 | OLE reduces α-synuclein aggregates toxicity favoring monomerization | [152] | |
| Micelle-bound α-synuclein | OLE aglycone prevents toxic interaction with lipids of α-synuclein N-terminal | [153] | |
| C. elegans models of PD | HTyr and OLE increase lifespan and inhibit the aggregation of α-synuclein | [154] | |
| C. elegans models of PD | HTyr increases lifespan and inhibits the aggregation of α-synuclein in muscle | [155] | |
| Diabetes neurodegeneration | db/db mice | HTyr improves mitochondrial function by activating PGC1α, AMPK, SIRT1 | [156] |
| STZ-treated rats | OLE restores spatial memory; decreases in hipp. SOD, IL-1β, TNF-α, p-mTOR | [157] | |
| STZ- and alloxan-treated rats | OLE has multiple actions against diabetes, e.g., on glucose tolerance | [158] | |
| Multiple sclerosis | EAE in rat | HTyr reduces lipid and protein oxidation, and increases glutathione peroxidase | [159] |
| LPS-activated rat astrocytes | HTyr inhibits pro-inflammatory enzymes gelatinases MMP-2 and MMP-9 | [160] | |
| EAE in rat | OLE increases SOD1/2, GPX1, SIRT1, anti-inflammatory M2 and decreases M1 | [161] | |
| Huntington’s disease | 3-nitropropionic acid in rats | HTyr and EVOO reduce lipid peroxidation and the decrease of GSH in striatum | [162] |
| Aging neurodegeneration | Aged mice (12-m-old) | HTyr (mix) restores brain ATP levels and improves spatial working memory | [126] |
Abbreviations: Adenosine triphosphate (ATP), tumor necrosis factor-alpha (TNF-α), long-term potentiation (LTP), silent mating type information regulation 2 homolog 2 (SIRT2), estrogen receptor β (Erβ), amyloid precursor protein (APP), 6-hydroxydopamine (6-OHDA), monoamine oxidase (MAO), β-amyloid (Aβ peptide), reactive oxygen species (ROS), nuclear factor E2-related factor 2 (Nrf2, also named NFE2L2), heme oxygenase-1 (HO-1), glutathione S-transferase (GSTs), NADPH quinone dehydrogenase 1 (NQO1), experimental autoimmune encephalomyelitis (EAE), 3,4-dihydroxyphenylacetaldehyde (DOPAL), glutathione/glutathione disulfide ratio (GSH/GSSG ratio), peroxisome proliferator-activated receptor coactivator 1α (PGC1α), AMP-activated kinase (AMPK), superoxide dismutase (SOD), interleukin 1β (IL-1β), phospho-mechanistic target of rapamycin (p-mTOR), matrix metalloproteinase 2 (MMP-2), streptozotocin (STZ).