Presenilin 1 increases association with synaptotagmin 1 during normal aging

NEUROBIOLOGY OF AGING

卷:86

Article

Keller, Laura J.^1,2  Sekula, Nicole M.¹  Svirsky, Sarah^1,3  Maesako, Masato¹  Zoltowska, Katarzyna M.^1,4  Berezovska, Oksana^1,2 

[1] Harvard Med Sch, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimers Dis Res Lab, Charlestown, MA USA

[2] MGH, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA

[3] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA

[4] Katholieke Univ Leuven, Dept Neurosci, VIB KU Leuven Ctr Brain & Dis Res, B-3000 Leuven, Belgium

关键词: Aging;    Presenilin 1;    Gamma secretase;    Synaptotagmin 1;    Alzheimer's disease;    Neuroscience;   

DOI  :  10.1016/j.neurobiolaging.2019.10.006

来源: Elsevier

【 摘 要 】

Presenilin 1 (PS1), the catalytic component of gamma secretase, associates with synaptotagmin 1 (Syt-1). This interaction is decreased in the brains of patients with sporadic Alzheimer's disease. However, it remains unclear how this interaction changes during normal aging. Because aging is a risk factor for Alzheimer's disease, we sought to identify changes in PS1 and Syt-1 association during aging in primary neurons in vitro and mouse brain sections ex vivo. We also tested the effect of aging on the calcium dependence of the interaction by treating neurons aged in vitro with KCl. We found that PSI and Syt-1 increase their association with age, an effect that is more robust in neuronal processes than cell bodies. Treatment with KCl triggered the interaction in both young and old neurons. Baseline calcium levels and calcium influx in response to KCl treatment were significantly higher in older neurons, which can partially explain the increase in PS1/Syt-1 binding with age. These results suggest a compensatory mechanism during normal aging to offset detrimental age-associated effects. (C) 2019 The Author(s). Published by Elsevier Inc.

【 授权许可】

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