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@ARTICLE{AgsBalboa:139531,
author = {Agís-Balboa, Roberto Carlos and Pinheiro, Paulo S and
Rebola, Nelson and Kerimoglu, Cemil and Benito, Eva and
Gertig, Michael and Bahari-Javan, Sanaz and Jain, Gaurav and
Burkhardt, Susanne and Delalle, Ivana and Jatzko, Alexander
and Dettenhofer, Markus and Zunszain, Patricia A and
Schmitt, Andrea and Falkai, Peter and Pape, Julius C and
Binder, Elisabeth B and Mulle, Christophe and Fischer, Andre
and Sananbenesi, Farahnaz},
title = {{F}ormin 2 links neuropsychiatric phenotypes at young age
to an increased risk for dementia.},
journal = {The EMBO journal},
volume = {36},
number = {19},
issn = {0261-4189},
address = {Hoboken, NJ [u.a.]},
publisher = {Wiley},
reportid = {DZNE-2020-05853},
pages = {2815-2828},
year = {2017},
abstract = {Age-associated memory decline is due to variable
combinations of genetic and environmental risk factors. How
these risk factors interact to drive disease onset is
currently unknown. Here we begin to elucidate the mechanisms
by which post-traumatic stress disorder (PTSD) at a young
age contributes to an increased risk to develop dementia at
old age. We show that the actin nucleator Formin 2 (Fmn2) is
deregulated in PTSD and in Alzheimer's disease (AD)
patients. Young mice lacking the Fmn2 gene exhibit PTSD-like
phenotypes and corresponding impairments of synaptic
plasticity, while the consolidation of new memories is
unaffected. However, Fmn2 mutant mice develop accelerated
age-associated memory decline that is further increased in
the presence of additional risk factors and is
mechanistically linked to a loss of transcriptional
homeostasis. In conclusion, our data present a new approach
to explore the connection between AD risk factors across
life span and provide mechanistic insight to the processes
by which neuropsychiatric diseases at a young age affect the
risk for developing dementia.},
keywords = {Adult / Age of Onset / Aging: genetics / Aging: physiology
/ Animals / Case-Control Studies / Dementia: epidemiology /
Dementia: genetics / Dementia: psychology / Formins / Humans
/ Male / Memory: physiology / Mice / Mice, Knockout /
Microfilament Proteins: genetics / Middle Aged / Nerve
Tissue Proteins / Neuronal Plasticity: genetics / Nuclear
Proteins: genetics / Phenotype / Risk Factors / Stress
Disorders, Post-Traumatic: complications / Stress Disorders,
Post-Traumatic: epidemiology / Stress Disorders,
Post-Traumatic: genetics / Formins (NLM Chemicals) /
Microfilament Proteins (NLM Chemicals) / Nerve Tissue
Proteins (NLM Chemicals) / Nuclear Proteins (NLM Chemicals)
/ formin 2 protein, mouse (NLM Chemicals)},
cin = {AG Sananbenesi / AG Fischer / AG Bonn 2},
ddc = {570},
cid = {I:(DE-2719)1410004 / I:(DE-2719)1410002 /
I:(DE-2719)1440012},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28768717},
pmc = {pmc:PMC5623844},
doi = {10.15252/embj.201796821},
url = {https://pub.dzne.de/record/139531},
}