Show simple item record

dc.contributor.authorBharadwaj, P.
dc.contributor.authorBates, K.
dc.contributor.authorPorter, T.
dc.contributor.authorTeimouri, E.
dc.contributor.authorPerry, G.
dc.contributor.authorSteele, J.
dc.contributor.authorGandy, S.
dc.contributor.authorGroth, David
dc.contributor.authorMartins, R.
dc.contributor.authorVerdile, G.
dc.date.accessioned2017-01-30T12:51:38Z
dc.date.available2017-01-30T12:51:38Z
dc.date.created2014-02-20T20:00:39Z
dc.date.issued2013
dc.identifier.citationBharadwaj, P.R. and Bates, K.A. and Porter, T. and Teimouri, E. and Perry, G. and Steele, J.W. and Gandy, S. and Groth, D. and Martins, R.N. and Verdile, Giuseppe. 2013. Latrepirdine: Molecular mechanisms underlying potential therapeutic roles in Alzheimer’s and other neurodegenerative diseases. Translational Psychiatry. 3 (e332): pp. 1-9.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/26082
dc.identifier.doi10.1038/tp.2013.97
dc.description.abstract

Latrepirdine (DimebonTM) was originally marketed as a non-selective antihistamine in Russia. It was repurposed as an effective treatment for patients suffering from Alzheimer’s disease (AD) and Huntington’s disease (HD) following preliminary reports showing its neuroprotective functions and ability to enhance cognition in AD and HD models. However, latrepirdine failed to show efficacy in phase III trials in AD and HD patients following encouraging phase II trials. The failure of latrepirdine in the clinical trials has highlighted the importance of understanding the precise mechanism underlying its cognitive benefits in neurodegenerative diseases before clinical evaluation. Latrepirdine has shown to affect a number of cellular functions including multireceptor activity, mitochondrial function, calcium influx and intracellular catabolic pathways; however, it is unclear how these properties contribute to its clinical benefits. Here, we review the studies investigating latrepirdine in cellular and animal models to provide a complete evaluation of its mechanisms of action in the central nervous system. In addition, we review recent studies that demonstrate neuroprotective functions for latrepirdine-related class of molecules including the β-carbolines and aminopropyl carbazoles in AD, Parkinson’s disease and amyotrophic lateral sclerosis models. Assessment of their neuroprotective effects and underlying biological functions presents obvious value for developing structural analogues of latrepirdine for dementia treatment.

dc.publisherNature.com
dc.subjectAlzheimer’s disease
dc.subjectmechanism of action
dc.subjectlatrepirdine
dc.titleLatrepirdine: Molecular mechanisms underlying potential therapeutic roles in Alzheimer’s and other neurodegenerative diseases
dc.typeJournal Article
dcterms.source.startPage1
dcterms.source.endPage9
dcterms.source.issn2158-3188
dcterms.source.titleTranslational Psychiatry
curtin.note

This article is published under the Open Access publishing model and distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by-nc-sa/3.0/. Please refer to the licence to obtain terms for any further reuse or distribution of this work.

curtin.department
curtin.accessStatusOpen access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record