Mechanisms Underlying Brain Aging Under Normal and Pathological Conditions / 神经科学通报·英文版

Aging is a major risk factor for many human diseases, including cognitive impairment, which affects a large population of the elderly. In the past few decades, our understanding of the molecular and cellular mechanisms underlying the changes associated with aging and age-related diseases has expanded greatly, shedding light on the potential role of these changes in cognitive impairment. In this article, we review recent advances in understanding of the mechanisms underlying brain aging under normal and pathological conditions, compare their similarities and differences, discuss the causative and adaptive mechanisms of brain aging, and finally attempt to find some rules to guide us on how to promote healthy aging and prevent age-related diseases.

Identifying interacting proteins of a Caenorhabditis elegans voltage-gated chloride channel CLH-1 using GFP-Trap and mass spectrometry / 生理学报

Chloride channels belong to a superfamily of ion channels that permit passive passage of anions, mainly chloride, across cell membrane. They play a variety of important physiological roles in regulation of cytosolic pH, cell volume homeostasis, organic solute transport, cell migration, cell proliferation, and differentiation. However, little is known about the functional regulation of these channels. In this study, we generated an integrated transgenic worm strain expressing green fluorescence protein (GFP) fused CLC-type chloride channel 1 (CLH-1::GFP), a voltage-gated chloride channel in Caenorhabditis elegans (C. elegans). CLH-1::GFP was expressed in some unidentified head neurons and posterior intestinal cells of C. elegans. Interacting proteins of CLH-1::GFP were purified by GFP-Trap, a novel system for efficient isolation of GFP fusion proteins and their interacting factors. Mass spectrometry (MS) analysis revealed that a total of 27 high probability interacting proteins were co-trapped with CLHp-1::GFP. Biochemical evidence showed that eukaryotic translation elongation factor 1 (EEF-1), one of these co-trapped proteins identified by MS, physically interacted with CLH-1, in consistent with GFP-Trap experiments. Further immunostaining data revealed that the protein level of CLH-1 was significantly increased upon co-expression with EEF-1. These results suggest that the combination of GFP-Trap purification with MS is an excellent tool to identify novel interacting proteins of voltage-gated chloride channels in C. elegans. Our data also show that EEF-1 is a regulator of voltage-gated chloride channel CLH-1.