On July 1, 2016, Prof. Monica Driscoll visited Institute of Biophysics, CAS and gave a lecture entitled “A Neat Approach to Neuroprotection: Throw Away the Trash”. The lecture was hosted by Prof. ZHANG Hong, and was part of the special lecture series named “BEI Shizhang Lecture” of Institute of Biophysics. 

Toxicity of misfolded proteins and mitochondrial dysfunction are pivotal factors that promote age-associated functional neuronal decline and neurodegenerative disease across species. Although these neurotoxic challenges have long been considered to be cell-intrinsic, evidence now supports that misfolded human disease proteins originating in one neuron can appear in neighboring cells, a phenomenon proposed to promote pathology spread. They have discovered and characterized a previously unknown capacity of C. elegans adult neurons to extrude large (~5μM) vesicles that include substantial amounts of cytoplasmic contents via a dynamic process.  These “exopher” vesicles can include fluorescent GFP or mCherry, loaded DiI, aggregated human proteins such as an expanded Q128 polyglutamine protein, human Alzheimer disease fragment A1-42, and/or mitochondria. Aggregated protein and oxidized mitochondria can be preferentially segregated into exophers. Inhibiting chaperone expression, autophagy, or the proteasome enhances exopher prevalence, as does ompromising mitochondrial quality, suggesting exopher-genesis as a response to stresses in proteostasis and organelle maintenance. Strikingly, extruded exopher contents can be found in both neighboring and remote cells. They suggest that “throwing out the trash” is a conserved mechanism that constitutes a fundamental, but formerly unrecognized, branch of neuronal proteostasis and mitochondrial quality control, which, when imbalanced, might actively contribute to the spread of neurotoxic species relevant to pathogenesis in human neurodegenerative disease and may be a factor in neuronal aging. 

Prof. Monica Driscoll gave the lecture with vivid words, rigorous logic and great passion, which can be a lively lesson for the audience. Investigators from Institute of Biophysics attending the lecture included Dr. YAN Xiyun, SUN Ming, CHEN Chang, ZHU Bing, XU Pingying and LIU Zhihua. After the lecture, Prof. Monica Driscoll and the audience shared their views on the issues of common interest.