Title
Autophagy in disease: a double-edged sword with therapeutic potential Autophagy in disease: a double-edged sword with therapeutic potential
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Colchester ,
Subject
Pharmacology. Therapy
Source (journal)
Clinical science. - Colchester
Volume/pages
116(2009) :9 , p. 697-712
ISSN
0143-5221
0009-9287
ISI
000265885600002
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Autophagy is a catabolic trafficking pathway for bulk destruction and turnover of long-lived proteins and organelles via regulated lysosomal degradation. In eukaryotic cells, autophagy occurs constitutively at low levels to perform housekeeping functions, such as the destruction of dysfunctional organelles. Up-regulation occurs in the presence of external stressors (e.g. starvation, hormonal imbalance and oxidative stress) and internal needs (e.g. removal of protein aggregates), suggesting that the process is an important survival mechanism. However, the occurrence of autophagic structures in dying cells of different organisms has led to the hypothesis that autophagy may also have a causative role in stress-induced cell death. The identification within the last decade of a full set of genes essential for autophagy in yeast, the discovery of human orthologues and the definition of signalling pathways regulating autophagy have accelerated our molecular understanding and interest in this fundamental process. A growing body of evidence indicates that autophagy is associated with heart disease, cancer and a number of neurodegenerative disorders, such as Alzheimer's, Parkinson's and Huntington's diseases. Furthermore, it has been demonstrated that autophagy plays a role in embryogenesis, aging and immunity. Recently, it has been shown that autophagy can be intensified by specific drugs. The pharmacological modulation of the autophagic pathway represents a major challenge for clinicians to treat human disease.
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