As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood-brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias.
Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug / J. Marschallinger, I. Schäffner, B. Klein, R. Gelfert, F.J. Rivera, S. Illes, L. Grassner, M. Janssen, P. Rotheneichner, C. Schmuckermair, R. Coras, M. Boccazzi, M. Chishty, F.B. Lagler, M. Renic, H. Bauer, N. Singewald, I. Blümcke, U. Bogdahn, S. Couillard-Despres, D.C. Lie, M.P. Abbracchio, L. Aigner. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 6(2015 Oct), pp. 8466.1-8466.16.
|Titolo:||Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug|
ABBRACCHIO, MARIA PIA (Penultimo)
|Parole Chiave:||biochemistry, genetics and molecular biology (all); chemistry (all); physics and astronomy (all)|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Progetto:||Imaging of Neuroinflammation in Neurodegenerative Diseases|
|Data di pubblicazione:||ott-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/ncomms9466|
|Appare nelle tipologie:||01 - Articolo su periodico|