Abstract | BACKGROUND: OBJECTIVE: The aim of the current study was to evaluate the potential of two tacrine- donepezil hybrid molecules (TA8Amino and TAHB3), which are AChE inhibitors, to induce neurodifferentiation and neuritogenesis in SH-SY5Y cells. METHODS: The experiments were carried out to characterize neurodifferentiation, cellular changes related to responses to oxidative stress and pathways of cell survival in response to drug treatments. RESULTS: The results indicated that the compounds did not present cytotoxic effects in SH-SY5Y or HepG2 cells. TA8Amino and TAHB3 induced neurodifferentiation and neuritogenesis in SH-SY5Y cells. These cells showed increased levels of intracellular and mitochondrial reactive oxygen species; the induction of oxidative stress was also demonstrated by an increase in SOD1 expression in TA8Amino and TAHB3-treated cells. Cells treated with the compounds showed an increase in PTEN(Ser380/Thr382/383) and AKT(Ser473) expression, suggesting the involvement of the AKT pathway. CONCLUSION: Our results demonstrated that TA8Amino and TAHB3 present advantages as potential drugs for AD therapy and that they are capable of inducing neurodifferentiation and neuritogenesis.
|
Authors | Natália Chermont Dos Santos Moreira, Jéssica Ellen Barbosa de Freitas Lima, Talita Perez Cantuaria Chierrito, Ivone Carvalho, Elza Tiemi Sakamoto-Hojo |
Journal | Journal of Alzheimer's disease : JAD
(J Alzheimers Dis)
Vol. 78
Issue 1
Pg. 353-370
( 2020)
ISSN: 1875-8908 [Electronic] Netherlands |
PMID | 32986667
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Amyloid beta-Peptides
- Cholinesterase Inhibitors
- MAPT protein, human
- Neuroprotective Agents
- Reactive Oxygen Species
- tau Proteins
- Donepezil
- Proto-Oncogene Proteins c-akt
- Acetylcholinesterase
- PTEN Phosphohydrolase
- PTEN protein, human
|
Topics |
- Acetylcholinesterase
(metabolism)
- Alzheimer Disease
(metabolism)
- Amyloid beta-Peptides
(metabolism)
- Cell Differentiation
(drug effects)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Cholinesterase Inhibitors
(therapeutic use)
- Donepezil
(therapeutic use)
- Humans
- Neurons
(drug effects)
- Neuroprotective Agents
- Oxidative Stress
(drug effects)
- PTEN Phosphohydrolase
- Phosphorylation
- Proto-Oncogene Proteins c-akt
(metabolism)
- Reactive Oxygen Species
(metabolism)
- tau Proteins
(metabolism)
|