ArticleJournal of Alzheimer's disease : JAD2012
Latrepirdine (dimebon) enhances autophagy and reduces intracellular GFP-Aβ42 levels in yeast.
Article in Journal of Alzheimer's disease : JAD, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 67 citations in OpenAlex.
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- Yeast as a Model for Human Disease.International journal of molecular sciences · 2026Review
- Regulation of autophagy-mediated pathways by diet, physical activity, and sleep in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Alzheimer's Disease: Significant Benefit from the Yeast-Based Models.International journal of molecular sciences · 2023Review
- The Effect of Calorie Restriction on Protein Quality Control in Yeast.Biomolecules · 2023Review
- The Use of Yeast in Biosensing.Microorganisms · 2022Review
- Pharmacological modulation of autophagy for Alzheimer's disease therapy: Opportunities and obstacles.Acta pharmaceutica Sinica. B · 2022Review
- Targeting autophagy in neurodegenerative diseases: From molecular mechanisms to clinical therapeutics.Clinical and experimental pharmacology & physiology · 2021Review
- Effects of A6E Mutation on Protein Expression and Supramolecular Assembly of Yeast Asparagine Synthetase.Biology · 2021Article
- A rapid absorbance-based growth assay to screen the toxicity of oligomer AβNeural regeneration research · 2020Article
- Activate or Inhibit? Implications of Autophagy Modulation as a Therapeutic Strategy for Alzheimer's Disease.International journal of molecular sciences · 2020Review
- Amylin and beta amyloid proteins interact to form amorphous heterocomplexes with enhanced toxicity in neuronal cells.Scientific reports · 2020Article
- Dl-3n-butylphthalide improves spatial learning and memory in rats with vascular dementia by reducing autophagy via regulation of the mTOR signaling pathway.Experimental and therapeutic medicine · 2020Article
- Application of yeast to studying amyloid and prion diseases.Advances in genetics · 2020Review
- Yeast Models for Amyloids and Prions: Environmental Modulation and Drug Discovery.Molecules (Basel, Switzerland) · 2019Review
- Autophagy Modulation as a Treatment of Amyloid Diseases.Molecules (Basel, Switzerland) · 2019Review
- Simvastatin Efficiently Reduces Levels of Alzheimer's Amyloid Beta in Yeast.International journal of molecular sciences · 2019Article
- Yeast Models for the Study of Amyloid-Associated Disorders and Development of Future Therapy.Frontiers in molecular biosciences · 2019Review
- Recent Insights on Alzheimer's Disease Originating from Yeast Models.International journal of molecular sciences · 2018Review
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Authors and funding
16 authors at 7 institutions in 3 countries.
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Abstract
Latrepirdine (Dimebon), an anti-histamine, has shown some benefits in trials of neurodegenerative diseases characterized by accumulation of aggregated or misfolded protein such as Alzheimer's disease (AD) and has been shown to promote the removal of α-synuclein protein aggregates in vivo. An important pathway for removal of aggregated or misfolded proteins is the autophagy-lysosomal pathway, which has been implicated in AD pathogenesis, and enhancing this pathway has been shown to have therapeutic potential in AD and other proteinopathies. Here we use a yeast model, Saccharomyces cerevisiae, to investigate whether latrepirdine can enhance autophagy and reduce levels of amyloid-β (Aβ)42 aggregates. Latrepirdine was shown to upregulate yeast vacuolar (lysosomal) activity and promote transport of the autophagic marker (Atg8) to the vacuole. Using an in vitro green fluorescent protein (GFP) tagged Aβ yeast expression system, we investigated whether latrepirdine-enhanced autophagy was associated with a reduction in levels of intracellular GFP-Aβ42. GFP-Aβ42 was localized into punctate patterns compared to the diffuse cytosolic pattern of GFP and the GFP-Aβ42 (19:34), which does not aggregate. In the autophagy deficient mutant (Atg8Δ), GFP-Aβ42 showed a more diffuse cytosolic localization, reflecting the inability of this mutant to sequester GFP-Aβ42. Similar to rapamycin, we observed that latrepirdine significantly reduced GFP-Aβ42 in wild-type compared to the Atg8Δ mutant. Further, latrepirdine treatment attenuated Aβ42-induced toxicity in wild-type cells but not in the Atg8Δ mutant. Together, our findings provide evidence for a novel mechanism of action for latrepirdine in inducing autophagy and reducing intracellular levels of GFP-Aβ42.
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