The intersection between growth factors, autophagy and ER stress: A new target to treat neurodegenerative diseases?

• Many neurodegenerative diseases are related to protein misfolding and aggregation.
• Autophagy is the main cellular process for removing such proteins aggregates.
• Autophagy impairment at different steps contribute to the neurodegenerative process.
• ER stress and growth factors participate in the modulation of this process.

One of the salient features of most neurodegenerative diseases is the aggregation of specific proteins in the brain. This proteostasis imbalance is proposed as a key event triggering the neurodegenerative cascade. The unfolded protein response (UPR) and autophagy pathways are emerging as critical processes implicated in handling disease-related misfolded proteins. However, in some conditions, perturbations in the buffering capacity of the proteostasis network may be part of the etiology of the disease. Thus, pharmacological or gene therapy strategies to enhance autophagy or UPR responses are becoming an attractive target for disease intervention. Here, we discuss current evidence depicting the complex involvement of autophagy and ER stress in brain diseases. Novel pathways to modulate protein misfolding are discussed including the relation between aging and growth factor signaling.This article is part of a Special Issue entitled SI:Autophagy.