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

被引:39
作者
Garcia-Huerta, Paula [1 ,2 ,3 ]
Troncoso-Escudero, Paulina [1 ,2 ,3 ]
Jerez, Carolina [1 ,2 ,4 ]
Hetz, Claudio [1 ,2 ,3 ,5 ]
Vidal, Rene L. [1 ,2 ,4 ]
机构
[1] Univ Chile, Biomed Neurosci Inst, Fac Med, Santiago, Chile
[2] FONDAP, Ctr Gerosci Brain Hlth & Metab, Santiago, Chile
[3] Univ Chile, Program Cellular & Mol Biol, Ctr Mol Studies Cell, Inst Biomed Sci, Independencia 1027, Santiago, Chile
[4] Neurounion Biomed Fdn, Santiago, Chile
[5] Harvard Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA
关键词
Autophagy; UPR; IGFs; ER stress; aggregation; neurodegenerative disease; UNFOLDED PROTEIN RESPONSE; AMYOTROPHIC-LATERAL-SCLEROSIS; CHAPERONE-MEDIATED AUTOPHAGY; ENDOPLASMIC-RETICULUM STRESS; TRANSCRIPTION FACTOR XBP1; N-TERMINAL TRIPEPTIDE; ALZHEIMERS-DISEASE; MOUSE MODEL; NEUROTROPHIC FACTOR; PARKINSONS-DISEASE;
D O I
10.1016/j.brainres.2016.02.052
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码:173 / 180
页数:8
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