Affiliations: [a]
Department of Physiology & Biophysics, State University of New York at Buffalo, Buffalo, NY, USA
| [b]
Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| [c] VA Western New York Healthcare System, Buffalo, NY, USA
Correspondence:
[*]
Correspondence to: Zhen Yan, PhD, Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 124 Sherman Hall, Buffalo, NY 14214, USA. E-mail: [email protected]
Correspondence:
[*]
Correspondence to: Shengdi Chen, MD, Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai, 200025, China. E-mail: [email protected].
Abstract: The loss of synaptic structure and function has been linked to the cognitive impairment of Alzheimer’s disease (AD). Dysregulation of the actin cytoskeleton, which plays a key role in regulating the integrity of synapses and the transport of synaptic proteins, has been suggested to contribute to the pathology of AD. In this study, we found that glutamate receptor surface expression and synaptic function in frontal cortical neurons were significant diminished in a familial AD (FAD) model, which was correlated with the reduction of phosphorylated cofilin, a key protein regulating the dynamics of actin filaments. Injecting a cofilin dephosphorylation inhibitory peptide to FAD mice led to the partial rescue of the surface expression of AMPA and NMDA receptor subunits, as well as the partial restoration of AMPAR- and NMDAR-mediated synaptic currents. Moreover, the impaired working memory and novel object recognition memory in FAD mice were partially ameliorated by injections of the cofilin dephosphorylation inhibitory peptide. These results suggest that targeting the cofilin-actin signaling holds promise to mitigate the physiological and behavioral abnormality in AD.
