Abstract:
Neurodegenerative illnesses are one of the main causes of disability in the aging population, representing a huge problem for society and healthcare systems. Although great progress has been made in understanding the biology of Alzheimer`s disease (AD), early detection and diagnosis of AD and other age-related neurodegenerative diseases remains a scientific challenge due to the heterogeneous nature of the disease. Here, I will discuss specifically the cutting-edge approaches, results, and the key difficulties that the field of neurodegeneration with relevance to redox-proteomics is currently confronted with. Redox proteomics in human AD and model systems is a result of the hypothesis that post-translational modifications can occur even to proteins that are modifiers themselves. The underlying idea is that brain is particularly vulnerable to oxidative damage because it consumes oxygen at a high rate. ROS are responsible for cellular damage in age-related neurodegenerative diseases. In fact, the ROS-induced Aß protein buildup in AD leads to lysosome membrane breakdown leading to neuronal death. Moreover, central role of astroglial alterations not only in late gliosis and neuroinflammation, but also in the early stages of AD led to the identification of a ‘triangle of death’ in AD brains, which consists of the aberrant crosstalk among energy metabolism, protein homeostasis and mTOR signaling. Clearly, there is a lot of work to be done in this area. I am curious to discover if oxidation of the same or other proteins occurs in other neurological disorders in addition to the concept of looking earlier in the evolution of AD. In this way, we can distinguish more specific markers of disease onset from markers of general processes such as neuronal damage. There are challenges still to be overcome, particularly in generating more complete maps of the proteome, and all of PTMs, emphasizing a framework of existing and potential therapeutic approaches.
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DOI:
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Published:
Journal: Abstract Book on 9th Annual Neuroscience Conference (ANC-23) August 12-13, 2023 , Volume: 0, Issue: 0, Year: 2023