Abstract
The elimination of abnormal and dysfunctional cellular constituents is an essential prerequisite for nerve cells to maintain their homeostasis and proper function. This is mainly achieved through autophagy, a process that eliminates abnormal and dysfunctional cellular components, including misfolded proteins and damaged organelles. Several studies suggest that age-related decline of autophagy impedes neuronal homeostasis and, subsequently, leads to the progression of neurodegenerative disorders due to the accumulation of toxic protein aggregates in neurons. Here, we discuss the involvement of autophagy perturbation in neurodegeneration and present evidence indicating that upregulation of autophagy holds potential for the development of therapeutic interventions towards confronting neurodegenerative diseases in humans.
Highlights
Autophagy is an evolutionarily conserved physiological process that facilitates decomposition of unnecessary or dysfunctional cytoplasmic components and organelles in the lysosome
We show evidence supporting the anti-ageing role of functional autophagy and we discuss the possible use of drugs enhancing autophagy for the treatment of age-related neurodegenerative diseases in humans
There is no clear evidence regarding the mechanistic link between ageing and neurodegenerative diseases, studies suggest that mitochondrial DNA mutations and oxidative stress are both causative agents for ageing and neurodegeneration [174,175]
Summary
Autophagy is an evolutionarily conserved physiological process that facilitates decomposition of unnecessary or dysfunctional cytoplasmic components and organelles in the lysosome. From yeasts to mammals, have identified more than 30 evolutionarily conserved autophagy-related genes (ATG), necessary for autophagy [2,3]. These genes are sequentially activated and facilitate the initiation, formation and elongation of the autophagosome, as well as its fusion with lysosome, for the generation of the autolysosome. Several studies show that autophagy decline in aged organisms might lead to neurodegeneration through impaired proteostasis and suggest genetic or pharmacological stimulation of autophagic components as putative therapies. We will present findings from research in animal model systems and humans supporting the assertion that dysfunctional autophagy and impaired proteostasis underlie, at least in part, the progression of the major neurodegenerative disorders. We show evidence supporting the anti-ageing role of functional autophagy and we discuss the possible use of drugs enhancing autophagy for the treatment of age-related neurodegenerative diseases in humans
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