Figure 1: SMERs as novel inducers of autophagy. | Nature Chemical Biology

Figure 1: SMERs as novel inducers of autophagy.

From: Stimulating the cell's appetite for itself

Figure 1

Certain proteins have the propensity to form protein aggregates, and excessive amounts of intracellular protein aggregates, as seen in neurodegenerative diseases, are cytotoxic. Under normal conditions, cells dispose of protein aggregates by wrapping them into a double-membraned phagophore (also called an isolation membrane), forming an autophagosome. When the autophagosome fuses with a lysosome, the hydrolytic enzymes of the latter degrade the protein aggregate and thus detoxify it. Autophagy is negatively regulated by the protein kinase TOR, which is also a positive regulator of cell growth. Inhibition of TOR with rapamycin therefore stimulates autophagy but also inhibits growth. The new compounds SMER10, SMER18 and SMER28 stimulate autophagy by a pathway that seems independent of TOR. Thus, these drugs could potentially be used to boost autophagy of protein aggregates in the nerve cells of people with neurodegenerative diseases, without the side effects associated with rapamycin.

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