Autophagy is an intracellular bulk degradation system.
The genetics, signalling and regulation of autophagy have been a major focus of research for the last decade and consequently these are increasingly well understood.
Defects in autophagy are now known to underpin a number of Mendelian human genetic diseases including multiple sulfatase deficiency, mucopolysaccharidosis type IIIA, X-linked myopathy with excessive autophagy, Danon disease, Pompe disease, and some forms of familial frontotemporal lobar degeneration. Autophagy may also be involved in familial forms of Parkinson’s disease. Furthermore, genome wide association studies are identifying autophagy as an important process underlying risk alleles for more complex polygenic diseases, such as Crohn’s disease.
Autophagy can be induced or inhibited by a number of physiological and pharmacological stimuli.
Manipulation of autophagy with drugs is a promising therapeutic strategy for a number of human genetic diseases characterised by aggregation of abnormal proteins. These diseases include polyglutamine diseases, such as Huntington’s disease and some familial forms of frontotemporal lobar degeneration and Parkinson’s disease. This is important, as there are currently no treatments which modify the rate of neurodegeneration in these conditions.