Gene therapy to target ER stress in brain diseases

Vicente Valenzuela, Gabriela Martínez, Claudia Duran-Aniotz, Claudio Hetz

Research output: Contribution to journalReview articlepeer-review

31 Scopus citations


Gene therapy based on the use of Adeno-associated viruses (AAVs) is emerging as a safe and stable strategy to target molecular pathways involved in a variety of brain diseases. Endoplasmic reticulum (ER) stress is proposed as a transversal feature of most animal models and clinical samples from patients affected with neurodegenerative diseases. Manipulation of the unfolded protein response (UPR), a major homeostatic reaction under ER stress conditions, had proved beneficial in diverse models of neurodegeneration. Although increasing number of drugs are available to target ER stress, the use of small molecules to treat chronic brain diseases is challenging because of poor blood brain barrier permeability and undesirable side effects due to the role of the UPR in the physiology of peripheral organs. Gene therapy is currently considered a possible future alternative to circumvent these problems by the delivery of therapeutic agents to selective regions and cell types of the nervous system. Here we discuss current efforts to design gene therapy strategies to alleviate ER stress on a disease context. This article is part of a Special Issue entitled SI:ER stress.

Original languageEnglish
Pages (from-to)561-570
Number of pages10
JournalBrain Research
StatePublished - 1 Oct 2016


  • Alzheimer's disease
  • Amyotrophic lateral sclerosis
  • Endoplasmic reticulum stress
  • Gene therapy
  • Parkinson's disease
  • Unfolded protein response


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