Effects Of Induction Of Autophagy In Cellular Models Of Neurodegenerative Diseases

Background: Neurodegenerative diseases share the common morphological characteristic of the deposition of abnormal proteins in the nervous system, including neurons. In chronic neurodegenerative diseases such as polyglutamine (polyQ) and Alzheimer disease (AD), commonly observed phenotypes include the abnormal accumulation of disease-causing proteins and the formation of nuclear and cytoplasmic inclusions. Under pathologic conditions, the accumulated level of such misfolded and toxic proteins may exceed the protective ability of the proteolytic machinery; the inability to either maintain misfolded proteins in a soluble form or degrade them results in their accumulation and the formation of inclusions. Autophagy refers to self-phagocytosis and is a process by which cells remove a large amount of proteins with long half-lives as well as damaged organelles. The mechanism of autophagy involves double-membraned autophagic vacuoles encapsulating the cytoplasm and organelles, and their fusion with lysosomes, resulting in the degradation of intracellular components.