Table 1.
Natural compounds and small molecules that modulate autophagic activity and control aggresome formation in AD models.
| Natural Compounds/Small Molecules |
AD Model | Molecular Mechanism |
Research Outcomes | References |
|---|---|---|---|---|
| Fisetin | Mouse and rat primary cortical neurons | mTOR inhibition, TFEB and Nrf2 activation |
Autophagy induction, decreases sarkosyl-insoluble tau phosphorylation | [111] |
| Ouabain | Tau transgenic fly, P301L mice | Inactivation of mTOR, activation of TFEB |
Increases autophagy, decreases toxic tau, increases memory function |
[112] |
| SLM, a carbazole-based fluorophore | 3xTg-AD | Activation of GSK-3β, reduces neuroinflammation | Decreases Aβ40 and Aβ42 levels, reduces phosphorylation of tau |
[109] |
| Aspirin | 5xFAD | Activation of PPARα and TFEB | Increases lysosomal biogenesis, decreases Aβ | [113] |
| Liraglutide | APP/PS1, APPswe/SH-SY5Y cells | Increase in IDE levels, mTOR-independent, JNK activation |
Improves cognitive function, reduces Aβ plaque deposition and inflammation, enhances LTP and autophagy activation |
[102,103] |
| Rapamycin | Transgenic (h)APP mice | mTOR inactivation | Improves memory, decreases sarkosyl-insoluble tau | [104,105] |
| Cinnamic acid | 5 × FAD | Activation of PPARα, upregulation of TFEB |
Reduces cerebral Aβ plaque burden, improves memory function, stimulates lysosomal biogenesis. | [114] |
| Trehalose | APP/PS1, Tg2576 | Increase in synaptophysin, doublecortin, and progranulin | Inhibits tau, improves cognitive and learning ability | [115,116] |
| Curcumin | APP/PS1 | mTOR inactivation | Reduces Aβ plaque, increases memory function | [106] |
| Oleuropein aglycone | TgCRND8 mice | Inhibition of mTOR and Ca2+ liberating | Reduces Aβ plaque, increases synaptic plasticity | [108] |
| Hep-14 | APP/PS1 | Upregulation of TFEB | Reduces Aβ plaque | [117] |
| Palm11-PrRP31 | APP/PS1 | Activation of pre-synaptic marker synaptophysin | Decreases Tau phosphorylation, reduces Aβ plaque and microgliosis |
[110] |
| Methylene blue | JNPL3 | mTOR inactivation | reduces insoluble tau, increases memory function | [107] |
| Temsirolimus | P301S mice | Inhibition of mTOR | Improves motor and memory function, reduces sarkosyl-insoluble tau | [118] |