Autophagy, One of the Main Steps in Periodontitis Pathogenesis and Evolution

Abstract

Periodontitis represents a complex inflammatory disease that compromises the integrity of the tooth-supporting tissue through the interaction of specific periodontal pathogens and the host's immune system. Experimental data help to outline the idea that the molecular way towards periodontitis initiation and progression presents four key steps: bacterial infection, inflammation, oxidative stress, and autophagy. The aim of this review is to outline the autophagy involvement in the pathogenesis and evolution of periodontitis from at least three points of view: periodontal pathogen invasion control, innate immune signaling pathways regulation and apoptosis inhibition in periodontal cells. The exact roles played by reactive oxygen species (ROS) inside the molecular mechanisms for autophagy initiation in periodontitis still require further investigation. However, clarifying the role and the mechanism of redox regulation of autophagy in the periodontitis context may be particularly beneficial for the elaboration of new therapeutic strategies.

Keywords: autophagy; oxidative stress; periodontitis.

Figure 1

Schematic representation of the possible mechanism of autophagy regulation in the periodontitis context. Autophagy can be modulated by ROS via four different pathways: (1) Atg12–Atg5 complex activation, promoting autophagy elongation; (2) ROS-dependent JNK induced Bcl-2 phosphorylation triggering Beclin 1 dissociation and autophagy induction; (3) PI3K-AKT pathway initiation triggering the activation of mTOR, which, in turn, acts as an autophagy induction inhibitor; and (4) the AMPK-dependent TORC1 activity inhibition leading to autophagy activation. Adapted from Liu C. et al. [51].