The Effects of Latrepirdine on Amyloid-β Aggregation and Toxicity

Journal of Alzheimer's Disease : JAD
T PorterGiuseppe Verdile

Abstract

Latrepirdine (Dimebon) has been demonstrated to be a neuroprotective and cognition improving agent in neurodegenerative diseases that feature protein aggregation and deposition, such as Alzheimer's disease (AD). The accumulation of amyloid-β (Aβ) protein aggregates is a key event in the neurodegenerative process in AD. This study explores if latrepirdine modulation of protein aggregation contributes to its neuroprotective mechanism of action. Assessment of neuronal cell death showed that there was a significant reduction in lactate dehydrogenase release at an equimolar ratio of Aβ:latrepirdine and with lower concentrations of latrepirdine. The ability of latrepirdine to alter the formation of Aβ42 aggregates was assessed by thioflavin-T fluorescence, western immunoblotting and atomic force microscopy (AFM). Despite showing a reduction in thioflavin-T fluorescence with latrepirdine treatment, indicating a decrease in aggregation, immunoblotting and AFM showed a modest increase in both the formation and size of Aβ aggregates. The discrepancies between thioflavin-T and the other assays are consistent with previous evidence that cyclic molecules can interfere with thioflavin-T binding of amyloid protein preparations. The ability of...Continue Reading

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Citations

Dec 25, 2019·Journal of Neurochemistry·Asta LučiūnaitėMichael T Heneka
Jul 21, 2020·Medicinal Research Reviews·Elena F ShevtsovaSergey O Bachurin
Mar 24, 2021·CNS Neuroscience & Therapeutics·Kirill ChaprovVladimir L Buchman

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Methods Mentioned

BETA
electrophoresis
Assay
atomic
AFM
fluorescence assay

Software Mentioned

Nova NT - MDT
SPSS Statistics

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