Poly-N-methylated Aβ-Peptide C-Terminal fragments (MEPTIDES) reverse the deleterious effects of amyloid-β in rats.

Authors:
Dr Adeola Shobo, PhD
Dr Adeola Shobo, PhD
McGill University
Dr
Montreal , McGill University | Canada

Metab Brain Dis 2018 04 9;33(2):387-396. Epub 2017 Oct 9.

College of Health Sciences, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.

Alzheimer's disease (AD) is characterized by extracellular deposition of amyloid-β (Aβ) plaques. These protein deposits impair synaptic plasticity thereby producing a progressive decline in cognitive function. Current therapies are merely palliative and only slow cognitive decline. Poly-N-methylated Aβ-Peptide C-Terminal Fragments (MEPTIDES) were recently shown to reduce Aβ toxicity in vitro and in Drosophila melanogaster, however whether these novel compounds are effective in inhibiting Aβ-induced toxicity in the mammalian brain remains unclear. We therefore investigated whether MEPTIDES have the ability to reduce the neurotoxic effects of Aβ in male Sprague-Dawley (SD) rats. Aβ42 (100 μg, 2 mM) or vehicle (0.15 M Tris buffer) was stereotaxically injected bilaterally into the dorsal hippocampus at a rate of 1 μl/min for 10 min. The effects on hippocampal-mediated learning were subsequently assessed using the Morris water maze (MWM). The presence of apoptotic activity was also assessed by determining the expression levels of active caspase-3 using real-time polymerase chain reaction and Western Blot techniques. In addition, half of the animals (n = 20) received an intraperitoneal (i.p.) injection of MEPTIDES (2 mg/kg) 48 h after intrahippocampal injection of Aβ42. Matrix-assisted laser desorption/ionization-time-of-flight (MALDI -TOF) mass spectrometry (MS) showed that MEPTIDES crossed the blood brain barrier (BBB) and revealed their distribution in the rat brain. Rats treated with Aβ42 displayed spatial learning deficits and increased hippocampal caspase-3 gene (CASP-3) expression which was reversed by subsequent injection of MEPTIDES. The present results show that MEPTIDES have the potential to reverse the toxic effects of Aβ42 in vivo.

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http://dx.doi.org/10.1007/s11011-017-0118-xDOI Listing
April 2018
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References

(Supplied by CrossRef)
Article in J Neurochem
R Akhter et al.
J Neurochem 2015
Article in Exp Neurol
A Awasthi et al.
Exp Neurol 2005
Article in Curr Pharm Des
C Balducci et al.
Curr Pharm Des 2014
Article in J Cell Mol Med
PR Bharadwaj et al.
J Cell Mol Med 2009
Article in Pharmacol Rev
SD Buckingham et al.
Pharmacol Rev 2009
Article in Peptides
DA Butterfield et al.
Peptides 2002
Article in Hong Kong Med J
L Chu et al.
Hong Kong Med J 2012
Article in Neurosci Biobehav Rev
M Colombo et al.
Neurosci Biobehav Rev 2000
Article in J Pineal Res
WM Daniels et al.
J Pineal Res 1998
Article in Metab Brain Dis
WM Daniels et al.
Metab Brain Dis 2001

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