6533b7d4fe1ef96bd1262974
RESEARCH PRODUCT
Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia
Andrea SchmittAndrea SchmittNelson RebolaNelson RebolaSusanne BurkhardtChristophe MulleChristophe MulleEva BenitoIvana DelalleRoberto Carlos Agis-balboaAlexander JatzkoGaurav JainPatricia A. ZunszainSanaz Bahari-javanPaulo S. PinheiroPaulo S. PinheiroPaulo S. PinheiroJulius C. PapeMarkus DettenhoferPeter FalkaiMichael GertigFarahnaz SananbenesiCemil KerimogluCemil KerimogluElisabeth B. BinderAndre FischerAndre Fischersubject
0301 basic medicineMalememoriaAginggenetics [Stress Disorders Post-Traumatic]Diseasegenetics [Neuronal Plasticity]BioinformaticsdemenciaStress Disorders Post-TraumaticMice0302 clinical medicineRisk FactorsNews & ViewsAge of OnsetMice KnockoutNeuronal PlasticitybiologyGeneral NeuroscienceMicrofilament ProteinsNuclear Proteinsgenetics [Nuclear Proteins]FearadultoMiddle AgedAlzheimer's diseasephysiology [Aging]Phenotype3. Good healthPhenotypemiedoFormin 2Forminsgenetics [Aging]estres postraumaticoepidemiology [Stress Disorders Post-Traumatic]AdultHDAC inhibidorpsychology [Dementia]alzheimerForminsNerve Tissue Proteinsepidemiology [Dementia]Affect (psychology)General Biochemistry Genetics and Molecular Biology03 medical and health sciencesHDAC inhibitorMemorygenetics [Dementia]ddc:570medicineDementiaAnimalsHumansenvejecimientoMolecular Biologyphysiology [Memory]General Immunology and MicrobiologyPost-traumatic stress disordermedicine.diseaseYoung age030104 developmental biologyformin 2 protein mouseCase-Control StudiesSynaptic plasticitybiology.proteinDementiagenetics [Microfilament Proteins]complications [Stress Disorders Post-Traumatic]030217 neurology & neurosurgeryHomeostasisdescription
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. Beca Ramón y Cajal GAIN- Agencia Gallega de Innovación
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-01-01 |