Investigator:
Athanasios Alexandris, MD
Name of Institution:
Johns Hopkins University School of Medicine
Project Title:
Investigating the role of a-synucleinopathy in axonal protein homeostasis and viability
Investigator Bio:
Dr. Athanasios Alexandris is a Research Associate in the Neuropathology division of the Department of Pathology at Johns Hopkins University School of Medicine. His research focuses on understanding the mechanisms of axonal degeneration and plasticity. Axons are the long processes of neurons essential for signal transmission in the brain. Axonal degeneration often precedes nerve cell loss in neurodegenerative diseases like Parkinson’s disease (PD) and current neuroprotective treatments that target neuronal cell bodies often fail to protect axons. Dr. Alexandris’s work aims to develop strategies for axonal protection, paving the way for novel treatments for neurodegenerative diseases like PD.
Dr. Alexandris earned his medical degree from the University of Leicester, UK, with an intercalated BSc in Neurosciences & Mental Health from Imperial College London. He conducted neuropathology research with the Neurodegenerative Pathology Research Group at Newcastle University and then pursued postdoctoral research at Johns Hopkins in the lab of Dr. Vassilis E. Koliatsos. Here, he integrated experimental neuropathology with advanced cellular and molecular techniques to investigate axonal injury and repair mechanisms, focusing on molecular pathways in trauma and neurodegenerative diseases.
Dr. Alexandris remains dedicated to advancing the understanding of axonal degeneration and repair, with the goal of translating his findings into innovative therapeutic strategies. His commitment reflects a deep-seated desire to improve outcomes for patients affected by neurodegenerative diseases.
Objective:
To explore how the abnormal alpha-synuclein (a-syn) protein, a key player in neurodegenerative diseases like PD and Dementia with Lewy bodies (DLB), affects axons—the nerve cell extensions that transmit brain signals.
Background:
Axonal degeneration is an early event in neurodegenerative disease, impairing brain connectivity before nerve cells die. To understand why axonal degeneration occurs, we are focused on how a-syn disrupts axonal localization and translation of mRNA, the template for producing proteins in axons which are crucial for their maintenance, plasticity, and repair.
Methods/Design:
We use human neurons derived from stem cells and mouse models to study the effects of a-syn on axonal mRNA localization and translation into proteins. In these models, a-syn fibrils simulate disease conditions. We then employ advanced techniques to isolate and sequence RNA from different parts of the nerve cells, such as axons. This approach allows us to pinpoint specific disruptions in mRNA localization and protein translation within axons caused by a-syn, shedding light on the molecular mechanisms underlying axonal vulnerability and early degeneration in PD and related diseases.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
We aim to uncover a link between abnormal a-syn and axonal survival and function. This may not only offer new ideas about why axons are vulnerable but may also reveal new mechanisms and targets for new therapies. These could include drugs aimed at preventing or reversing axonal dysfunction, leading to more effective treatments for PD and related disorders.