Dysregulation of cofilin-1 activity—the missing link between herpes simplex virus type-1 infection and Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a multifactorial disease triggered by environmental factors in combination with genetic predisposition. Infectious agents, in particular herpes simplex virus type 1 (HSV-1), are gradually being recognised as important factors affecting the development of AD. However, the mechanism linking HSV-1 and AD remains unknown. Of note, HSV-1 manipulates the activity of cofilin-1 to ensure their efficient infection in neuron cells. Cofilin-1, the main regulator of actin cytoskeleton reorganization, is implicating for the plastic of dendritic spines and axon regeneration of neuronal cells. Moreover, dysfunction of cofilin-1 is observed in most AD patients, as well as in mice with AD and ageing. Further, inhibition of cofilin-1 activity ameliorates the host cognitive impairment in an animal model of AD. Together, dysregulation of cofilin-1 led by HSV-1 infection is a potential link between HSV-1 and AD. Herein, we critically summarize the role of cofilin-1-mediated actin dynamics in both HSV-1 infection and AD, respectively. We also propose several hypotheses regarding the connecting roles of cofilin-1 dysregulation in HSV-1 infection and AD. Our review provides a foundation for future studies targeting individuals carrying HSV-1 in combination with cofilin-1 to promote a more individualised approach for treatment and prevention of AD.

Keywords:

• Cofilin-1
• actin cytoskeleton
• Alzheimer’s disease
• cognitive impairment
• HSV-1

Author contributions

Yiliang Wang, Xiaowei Song, and Yun Wang: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; Lianzhou Huang, Yun Wang, Shurong Qin, and Feng Li: collection and/or assembly of data, data analysis and interpretation; Fujun Jin, Zhe Ren, and Yifei Wang: conception and design, manuscript writing, final approval of manuscript. All authors read and approved the final manuscript. Yiliang Wang and Xiaowei Song contributed equally to this manuscript.

Disclosure statement

The authors have no conflicts of interest to declare.

Additional information

Funding

This work was supported by Grants from the National Natural Science Foundation of China [No.81872908 and 81573471], the Science and Technology Programme of Guangzhou, China [201604020178], and Key Projects of Biological Industry Science & Technology of Guangzhou China [grant number 201300000060], and Science & Technology Plan Programme of Guangdong Province China [grant number 2012A080204003].