Rab7 may be a novel therapeutic target for neurologic diseases as a key regulator in autophagy

J Neurosci Res. 2017 Oct;95(10):1993-2004. doi: 10.1002/jnr.24034. Epub 2017 Feb 10.

Abstract

Macroautophagy is an evolutionally conserved membrane trafficking pathway that delivers intracellular materials to lysosomes for degradation and recycling. Rab7, as a member of the Rab GTPase superfamily, has a unique role in the regulation of macroautophagy, especially in modulating autophagy flux. The functional states of Rab7 generally switch between GTP-bound and GDP-bound states under the control of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Activated GTP-Rab7 is capable of regulating autophagosome formation, autophagosome transportation along microtubules, endosome and autophagosome maturation, as well as lysosome biogenesis via interacting with its effector molecules. Rab7-mediated macroautophagy is closely associated with various pathological processes of several neurologic diseases, such as Parkinson's disease, Huntington's disease, Alzheimer's disease, Charcot-Marie-Tooth type 2B disease, and cerebral ischemic diseases. Considering that macroautophagy can be the prime therapeutic target in certain nervous system diseases, in-depth study of Rab7 in the regulation of macroautophagy may be helpful to identify novel strategies for the treatment of autophagy-related neurologic diseases. © 2017 Wiley Periodicals, Inc.

Keywords: Rab7; autophagosome maturation; autophagy; neurologic diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagy / physiology*
  • Humans
  • Nervous System Diseases / metabolism*
  • Nervous System Diseases / pathology*
  • rab GTP-Binding Proteins / metabolism*
  • rab7 GTP-Binding Proteins

Substances

  • rab7 GTP-Binding Proteins
  • rab7 GTP-binding proteins, human
  • rab GTP-Binding Proteins