Pharmacological and genetic reversal of age-dependent cognitive deficits attributable to decreased presenilin function.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Sean M J McBrideThomas A Jongens

Abstract

Alzheimer's disease (AD) is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are attributable to mutations in a single copy of the Presenilin (PS) and amyloid precursor protein genes. The dominant inheritance pattern of FAD indicates that it may be attributable to gain or change of function mutations. Studies of FAD-linked forms of presenilin (psn) in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of Drosophila metabotropi...Continue Reading

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Citations

Nov 1, 2013·Psychopharmacology·Sébastien JacquemontBaltazar Gomez-Mancilla
Jul 3, 2015·Molecular Medicine Reports·Zeng-Zhang ZhengHong-Sheng Song
Dec 15, 2015·Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology·A J BerensA L Toth
Apr 24, 2012·Journal of Peptide Science : an Official Publication of the European Peptide Society·Claudia KunzHans-Jörg Hofmann
Sep 25, 2015·Journal of Alzheimer's Disease : JAD·Mansi R Khanna, Mark E Fortini
Nov 14, 2014·ELife·Till F M AndlauerStephan J Sigrist
Jul 10, 2019·Genes, Brain, and Behavior·Dova B Brenman-SuttnerAnne F Simon
Mar 3, 2011·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Janusz K Rybakowski
Sep 19, 2018·Molecular Neurobiology·Cara J Westmark

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