Impaired Autophagy in Neurodegenerative Disorders

Impaired Autophagy in Neurodegenerative Disorders

By Dr Ananya Mandal, MD

WHAT IS AUTOPHAGY?

The word autophagy is derived from Greek words “auto” meaning self and “phagy” meaning eating. Autophagy is a normal physiological process in the body that deals with destruction of cells in the body.

It maintains homeostasis or normal functioning by protein degradation and turnover of the destroyed cell organelles for new cell formation.

During cellular stress the process of Autophagy is upscaled and increased. Cellular stress is caused when there is deprivation of nutrients and/or growth factors.

Thus Autophagy may provide an alternate source of intracellular building blocks and substrates that may generate energy to enable continuous cell survival.

Autophagy also kills the cells under certain conditions. These are form of programmed cell death (PCD) and are called autophagic cell death. Programmed cell death is commonly termed apoptosis.

AUTOPHAGY IN DOWN SYNDROME

Autophagy is termed a nonapoptotic programmed cell death with different pathways and mediators from apoptosis.

Autophagy mainly maintains a balance between manufacture of cellular components and break down of damaged or unnecessary organelles and other cellular constituents.

There are some major degradative pathways that include proteasome that involves breaking down of most short-lived proteins.

Autophagy and stress

Autophagy enables cells to survive stress from the external environment like nutrient deprivation and also allows them to withstand internal stresses like accumulation of damaged organelles and pathogen or infective organism invasion.

Autophagy is seen in all eukaryotic systems including fungi, plants, slime mold, nematodes, fruit flies and insects, rodents (laboratory mice and rats), humans.

Types of autophagy

There are several types of Autophagy. These are:-

microautophagy – in this process the cytosolic components are directly taken up by the lysosome itself through the lysosomal membrane.
macroautophagy – this involves delivery of cytoplasmic cargo to the lysosome through the intermediary of a double membrane-bound vesicle. This is called an autophagosome that fuses with the lysosome to form an autolysosome.
Chaperone-mediated autophagy – in this process the targeted proteins are translocated across the lysosomal membrane in a complex with chaperone proteins (such as Hsc-70).
micro- and macropexophagy
piecemeal microautophagy of the nucleus
cytoplasm-to-vacuole targeting (Cvt) pathway

Reviewed by April Cashin-Garbutt, BA Hons (Cantab)