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.