Autophagy in neurodegenerative diseases: pathogenesis and therapy

Abstract

The most prevalent pathological features of many neurodegenerative diseases are the aggregation of misfolded proteins and the loss of certain neuronal populations. Autophagy, as major intracellular machinery for degrading aggregated proteins and damaged organelles, has been reported to be involved in the occurrence of pathological changes in many neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. In this review, we summarize most recent research progress in this topic and provide a new perspective regarding autophagy regulation on the pathogenesis of neurodegenerative diseases. Finally, we discuss the signaling molecules in autophagy-related pathways as therapeutic targets for the treatment of these diseases.

Keywords: autophagy; neurodegenerative diseases; protein aggregation.

Figure 1

Autophagy induction and autophagosome formation. This diagram shows the process of autophagy induction and roles of Atg related proteins in autophagosome formation.

Figure 2

Overview of autophagic flux and impaired states in neurodegenerative diseases. This schematic diagram shows the procedures through the autophagic flux from formation of the autophagosome to fusion with the lysosome. Red text highlights refer to the dysfunctional steps in autophagy, along with related neurodegenerative diseases. Arrows' directions stand for activation or inhibition.

Figure 3

Molecular targets of autophagy up‐regulating agents. This schematic diagram shows representative molecular agents involved in autophagy activation through regulating autophagy‐related pathways. Either the mTOR‐dependent or mTOR‐independent pathway could play a negative role in autophagy. In addition, suppression of these pathways will result in activation of autophagy.