Seminar at the National Institute of Immunology.

On April 17th, I went to the National Institute of Immunology (NII) to attend a seminar series on "Immunological mechanisms of resilience in the brain". The speaker in the seminar was a professor from Yale School of Medicine, Prof. Carla Rothlin. She is the Dorys McConnell Duberg Professor of Immunobiology and Professor of Pharmacology. The seminar was conducted in seminar room 1 in the NII main building. Started at 4 p.m. and went on for around 1 hour and 30 minutes.

The main crux of the lecture is to address the role of the immune system in countering various diseases in our brain. The lecture was divided into two parts: Part 1 is about the retina, and Part 2 is about Alzheimer's disease. She started her lecture by covering the immune aspect of vision. She addressed the role of Retinal Pigmented Epithelium in maintaining visual function and the visual cycle. Retinal pigmented epithelial cells are phagocytic, with the ability to engulf and eliminate exfoliated POS(Photoreceptor Outer Segments) and maintain the normal renewal of visual cells. She told us about a gene named MERTK (MER proto-oncogene tyrosine kinase) that encodes a protein called MerTK, which is a receptor tyrosine kinase involved in the regulation of phagocytosis and inflammation. In the retina, MerTK is expressed in Retinal Pigmented Epithelial cells and is essential for the proper functioning of the visual system. The role of MerTK in the retina is primarily related to the phagocytosis of Photoreceptor Outer Segments(POS) by RPE cells. POS are shed daily by photoreceptor cells and are engulfed and degraded by RPE cells to maintain the health and integrity of the retina. MerTK mediates the recognition and binding of POS by RPE cells, and its activity is necessary for efficient phagocytosis and clearance of POS. In the absence of MerTK and tyrosine, inflammation occurs in RPE cells, which leads to a disease called Retinitis Pigmentosa. She told us that if we want to analyse the activity of RPE cells, then an electroretinogram is the gold standard.

Prof. Carla Rothlin

In the next lecture, she discussed one of the most dreaded diseases in the world, Alzheimer's disease. Alzheimer's is a progressive and degenerative neurological disorder that affects the brain, causing memory loss and cognitive decline. It’s is the most common form of dementia. Alzheimer's is considered a deadly and silent killer because it is a progressive disease that can slowly and gradually affect the brain over several years or even decades before the symptoms become noticeable. In the early stages, the symptoms may be mild and slightly overlooked, as they can be mistaken for normal signs of ageing.  The talk was about the Aß Hypothesis in Alzheimer's, which basically states that the accumulation and decomposition of oligomeric or fibrillar amyloid beta peptide is the primary cause of Alzheimer’s disease. She particularly pressed on the matter of microglial cells. Then she talked about the influence of gliosis in Alzheimer's. Gliosis is a process in which glial cells in the central nervous system, particularly astrocytes, undergo a reactive change in response to injury or disease. During gliosis, astrocytes and other glial cells become hypertrophic or enlarged and proliferate to form a glial scar. The glial scar acts as a physical barrier that isolates the damaged tissue and prevents further damage from occurring. Although the point to be noted is that proliferation and activation of microglia in the brain, concentrated around amyloid plaques, is a prominent feature of Alzheimer's, The majority of the risk genes for Alzheimer's disease are highly expressed (or selectively expressed) in microglial cells in the brain. On the contrary, there is mounting evidence that microglia protect against the incidence of Alzheimer's since impaired microglial activities and altered microglial responses to ß-amyloid are associated with increased Alzheimer's disease risk. Microglia can mediate synapse loss by engulfing synapses, likely via a complement-dependent mechanism; they can also intensify tau pathology and secrete inflammatory factors that can injure neurons directly or via activation of neurotoxic astrocytes.

Also, I had a question since we know that ß-amyloid plaque is one of the major causes of Alzheimer's. The ß-amyloid plaque is formed due to the misfolding of polypeptide chains. So misfolding of a protein causes the accumulation of these fibrils, which finally get accumulated in the brain as plaques. So can we stop or troubleshoot the formation of the amyloid fibrils in the first place before they get accumulated in the brain? Is there any targeted drug delivery, or can we, like, have a program through which we can detect those misfoldings and somehow unfold that misfolded protein into its primary structure?

Overall, the seminar was amazing. Got a lot to learn.