Table 1.
Examples of evidence for beneficial effect of autophagy stimulation in murine brain.
| Compound |
Targeted pathway |
Ectopic expression |
Disease model |
Outcome | References |
|---|---|---|---|---|---|
| Rapamycin | Mammalian target of rapamycin (mTor) |
Human TDP-43 | Amyotrophic lateral sclerosis | Reduced TDP-43 inclusions and improved learning/memory impairment | (56) |
| Rapamycin | mTor | Human APP Human TAU Human PSEN1 |
Alzheimer's disease | Reduced beta-amyloid and TAU deposition and improved learning defects | (57) |
| Rapamycin | mTor | Human NACP | Parkinson's disease | Reduced aggregation of NACP and associated pathology | (58) |
| CCI-779 | mTor | Human HTT | Huntington's disease | Reduced huntingtin aggregates formation and improved behavioral phenotype | (59) |
| Trehalose | mTor-independent | Human SOD1 | Amyotrophic lateral sclerosis | Reduced accumulation of SOD1 and enhanced motoneuronal survival | (60) |
| Trehalose | mTor-independent | Human APP Human PSEN1 |
Alzheimer's disease | Reduced beta-amyloid plaque deposition and improved learning defects | (61) |
| Trehalose | mTor-independent | Human TAU | Alzheimer's disease | Reduced TAU inclusions and increased brain neuronal survival | (62) |
| Trehalose | mTor-independent | Human HTT | Huntington's disease | Reduced formation of polyglutamine aggregates and amelioration of motor dysfunction | (63) |
| Lithium | Inositol synthesis | Human APP Human PSEN1 |
Alzheimer's disease | Reduced beta-amyloid plaque formation and improved memory deficits | (64) |
| Lithium | Inositol synthesis | Human SOD1 | Amyotrophic lateral sclerosis | Reduced SOD1 aggregates and increased brain neuronal survival | (65) |
| Carbamazepine | Inositol synthesis | Human APP Human PSEN1 |
Alzheimer's disease | Reduced beta-amyloid plaque formation and improved memory deficits | (66) |
| Carbamazepine | Inositol synthesis | Human TDP-43 | Amyotrophic lateral sclerosis | Reduced TDP-43 inclusions and improved learning/memory impairement | (56) |
| Spermidine | Acetyl transferases synthesis | Human TDP-43 | Amyotrophic lateral sclerosis | Reduced TDP-43 inclusions and improved learning/memory impairement | (56) |
| Verapamil | Ca2+ channel | Human SOD1 | Amyotrophic lateral sclerosis | Reduced SOD1 aggregates and prolonged animal survival | (67) |
| Felodipine | Ca2+ channel | Human NACP | Parkinson's disease | Reduced aggregation of NACP and improved behavioral phenotype | (68) |
| Calpastatin | Calpain | Human HTT | Huntington's disease | Reduced HTT aggregates formation and improved locomotor function | (69) |
| Beclin-1 | Beclin-1 dependent | Human NACP | Parkinson's disease | Reduced aggregation of NACP | (70) |
| LAMP2A | LAMP2A dependent | Human NACP | Parkinson's disease | Reduced generation of aberrant NACP species | (71) |