Advances in genetics research in the pathogenesis of amyotrophic lateral sclerosis / 中南大学学报(医学版)

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease affecting the upper and lower motor neurons. It is characterized by progressive muscle weakness, atrophy and ultimate death due to dysphagia and dyspnea. There are many causes of ALS, among which the genetic factors show great relevance. Imbalance of protein homeostasis in neurons, prion-like proliferation and propagation of abnormal proteins, mitochondrial dysfunction, glutamate mediated excitotoxicity, and intraneuronal substance transport disorders are recognized as the pathogenesis.The study on gene mutation related to pathogenesis will bridge the molecular and cellular research of ALS, which can deepen the understanding of the occurrence and development of ALS and the role of gene mutation in ALS, and provide new ideas and enlightenment for the treatment of ALS.

A Common Immunopathogenesis Mechanism for Infectious Diseases: The Protein-Homeostasis-System Hypothesis / 감염과화학요법

It was once believed that host cell injury in various infectious diseases is caused solely by pathogens themselves; however, it is now known that host immune reactions to the substances from the infectious agents and/or from the injured host cells by infectious insults are also involved. All biological phenomena in living organisms, including biochemical, physiological and pathological processes, are performed by the proteins that have various sizes and shapes, which in turn are controlled by an interacting network within the living organisms. The author proposes that this network is controlled by the protein homeostasis system (PHS), and that the immune system is one part of the PHS of the host. Each immune cell in the host may recognize and respond to substances, including pathogenic proteins (PPs) that are toxic to target cells of the host, in ways that depend on the size and property of the PPs. Every infectious disease has its own set of toxic substances, including PPs, associated with disease onset, and the PPs and the corresponding immune cells may be responsible for the inflammatory processes that develop in those infectious diseases.

Ubiquitin Ligases in Cholesterol Metabolism

To maintain cholesterol homeostasis, the processes of cholesterol metabolism are regulated at multiple levels including transcription, translation, and enzymatic activity. Recently, the regulation of protein stability of some key players in cholesterol metabolism has been characterized. More and more ubiquitin ligases have been identified including gp78, Hrd1, TRC8, TEB4, Fbw7, and inducible degrader of low density lipoprotein receptor. Their working mechanisms and physiological functions are becoming revealed. Here, we summarize the structure, substrates and function of these ubiquitin ligases. Their potential application in drug discovery is also discussed.