Mitophagy in Neurodegeneration: An Opportunity for Therapy?

R.      X. Santos; S.      C. Correia; C.      Carvalho; S.      Cardoso; M.      S. Santos; P.      I. Moreira

Abstract

Neurodegenerative disorders such as Alzheimers and Parkinsons diseases are characterized by distinct clinical manifestations and neuropathological hallmarks, but they also share common features like mitochondrial dysfunction. As strategic organelles in several cellular pathways, including life/death decision, it is crucial to maintain a healthy mitochondrial pool to ensure cellular homeostasis. Macroautophagy is a pathway of lysosomal-dependent degradation of cytosolic portions, such as misfolded proteins or damaged organelles. In the last decade this process has gained new frontiers and is currently seen as a specific, rather than a random process. In this regard the term mitophagy came to describe the selective degradation of mitochondria by autophagy. This review is intended to discuss mitochondrial dysfunction in Alzheimers and Parkinsons diseases. The recent developments on the molecular basis of mitophagy will be also argued. Finally, we will discuss mitophagy as a potential therapeutic target for neurodegenerative diseases.

Keywords: Mitochondrial dysfunction, Alzheimer's disease, Parkinson's disease, mitophagy, potential therapy, neurodegeneration, oxidative injury, ROS, autophagy, pathophysiology