Understanding progression of neuroinflammatory diseases via the tryptophan metabolism

Abstract

Tryptophan is one of the 10 essential amino acids, its metabolism is involved in the regulation of physiological functions such as protein synthesis and regulation of the serotonin-melatonin pathway, thereby, affecting mood, behaviour, sleep and circadian rhythms. Modulation of the Kynurenine-NAD pathway (collectively known as KP) affects energy balance, brain activity, and immune activation. Accordingly, the study of KP metabolites (KP metabolomics) is an emerging field of research particularly in the area of neuroinflammation and neurodegeneration.

Research advancements in immunology show that the KP is highly active, and is competitive with the serotonin pathway for tryptophan during inflammatory processes. Some of the metabolites that are produced downstream when the KP is activated include kynurenic acid and quinolinic acid which are neuroactive molecules capable of affecting neurotransmission by interacting with the N-methyl-D-Aspartate receptor. Imbalances in these two molecules have been demonstrated to induce excitotoxicity in several neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and amyotrophic lateral sclerosis. Hence, prolonged disruption of tryptophan metabolism due to neuroinflammation can have overall detrimental consequences such as cognitive fatigue, brain excitotoxicity, depression, and sleep disturbance that are common symptoms in many of these diseases.

In this talk, Prof Guillemin will highlight the roles of the tryptophan metabolism especially KP in neurodegenerative diseases. He will showcase some of his previous works performed on human primary cells to demonstrate how environmental exposure (e.g. biotoxin) can elicit inflammatory processes leading to interaction with the KP to cause disruption to normal brain cell activities as a disease model in various neurodegenerative diseases. 

Bio

Professor Gilles J. Guillemin been working in the field of Neuroinflammation for more than 24 years and in the field of tryptophan metabolism for 20 years. He is currently co-leading a new MND research and Neurodegenerative diseases Centre at Macquarie University (Since November 2012). He is studying the involvement of the tryptophan catabolism (via the kynurenine pathway) in human neurodegenerative diseases. He demonstrated the importance of the kynurenine pathway in multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis, which opens numerous very promising research opportunities and has important therapeutic potential. He also extended my research to other diseases such as depression, autism and brain tumours. These have been the focus of national and international collaborations that have led to several grants.

Professor Guillemin’s research output in the last 5 years has included 135 original research publications and has received over 9000 citations. This represents more than half of my career publications and citations. The quality of his recent research has led to reports in top rating journals including Nature (x2), Nature Communications, Scientific Reports (x2), Progress in Neurobiology, Oncotarget (x3), Lancet Psychiatry and Cancer Research (x2). Most significantly he initiated and drove many of these studies, as evidenced by his senior or co-authorship status in 52 of the reports since 2012. His annual citation rate has more than doubled since 2012 to >1500 pa. His h-index is 50. His current Researchgate score (46.25 – top 2.5% scientist worldwide) is growing every month with presently more than 250 profile view per week.