Inhibitory peptides to control autophagy

23 August 2018

The new peptides can be used to occlude autophagy in living animals, a key to treat various brain disorders.

Autophagy, meaning "self-eating" in Greek, is a general metabolic mechanism adopted by nearly all the eukaryotic species, from the single cell yeast to humans. It is a process that cells degrade unnecessary components for materials recycling and energy generation to survive against stress or maintain homeostasis.

On the good side, autophagy can protect cells by eliminating harmful materials (for example amyloid aggregates in neurodegenerative diseases and pathogen invasions), but defects in autophagy are often related to many diseases, such as Alzheimer's diseases or Parkinson diseases. In case of tumours, the autophagy pathway can be hijacked to supply enough nutrients for their massive growth. As a result, either activating or inhibiting autophagy in a controlled manner could be a promising treatment against various kinds of diseases.

Professor Mingjie Zhang (Croucher Senior Research Fellowship 2018 and 2003) is a structural biologist who has made numerous contributions to the elucidation of structural and regulatory properties of neuronal signalling proteins.

In his recent research, he has discovered potent and specific inhibitory peptides to target the Atg8 family, the central components in the autophagy pathway. These peptides can be used to occlude autophagy in living animals, which could be the key to treat various brain disorders.

The new peptides can also block autophagy in cultured monkey kidney tissue at a given time and a given location. "The strong Atg8 binding peptides are genetically encodable and can be expressed in tissue of living animals, in contrast to small molecule-based drugs in existing autophagy research,” Zhang added.

Professor Hong Zhang from Institute of Biophysics, Chinese Academy of Science noted, “the distinct function of these peptides in the autophagy pathway is still a wide-open area. Their functions are always masked by their early effect or redundancy. The peptides developed here probably will serve as a great tool to dissect the different roles of these two sub-families of Atg8 proteins in autophagy."

Zhang hopes that the peptides can serve as leads to develop drugs for potential cancer treatments and as a research tool to look for autophagy inducers for treating neurodegenerative diseases.

Professor Mingjie Zhang obtained his bachelor’s degree in chemistry from Fudan University, Shanghai in 1988, and his Ph.D. degree in Biochemistry in the University of Calgary, Canada in 1994. After a brief postdoctoral training in the Ontario Cancer Institute, Toronto, Canada, he established his own laboratory as an Assistant Professor in the Department of Biochemistry, The Hong Kong University of Science and Technology (HKUST) in 1995. Prof Zhang is currently a Kerry Holdings Professor of Science, Senior Fellow of the Institute for Advanced Study, and Chair Professor in the Division of Life Science, HKUST.

To view Professor Zhang's Croucher profile, please click here