TITLE:
Subcutaneous Sustained-Release of Poly-Arginine Ameliorates Cognitive Impairment in a Transgenic Mouse Model of Alzheimer’s Disease
AUTHORS:
Gennadiy Fonar, Baruh Polis, Tomer Meirson, Alexander Maltsev, Abraham O. Samson
KEYWORDS:
L-Arginine, Memory, LTP, Amyloid Beta, Cytotoxicity, Apoptosis
JOURNAL NAME:
Advances in Alzheimer's Disease,
Vol.7 No.4,
December
20,
2018
ABSTRACT: Poly-arginine peptides are a
promising class of bioactive compounds that are capable of crossing the
blood-brain barrier (BBB) and present neuroprotective properties. In this
study, we test the activity of poly-arginine peptides in a triple-transgenic
mouse model of Alzheimer’s disease. To identify the best candidate, we examined the relative
neuroprotective efficacy of the compounds with various lengths (R7, R9, and
R11) via assessment of memory acquisition, long-term hippocampal potentiation
(LTP), and cytotoxicity. Also, we explored the expression profiles of hundreds
of key cell signaling proteins, and perform a high content antibody microarray
comparative analysis of brain samples. The chronically treated animals with
poly-arginine R9 show significantly improved acquisition of memory. This
compound rescues hippocampal LTP deteriorated by Aβ at a better rate than other agents tested in this study and
induces cellular pathways involved in neuroprotection and neuroplasticity. The
treatment escalates the expression levels of Synapsin Ia in the mice
hippocampi; however, it has no significant effect upon the rate of
beta-amyloidosis. Poly-arginine R9 peptide is a well-tolerated compound that
crosses the BBB and presents unique neuroprotective qualities. The substance
halters the development of AD symptoms in a murine model and can be recommended
for clinical investigation.