Studentship

Diego Manni

p62 in age-related neurodegenerative

Neurodegenerative diseases are devastating, terminal and incurable conditions with ever-increasing burden on public health services.

This project is aiming at identification of potential molecular targets that could offer an opportunity for amelioration of these diseases.

One of such potential targets is an essential molecular pathway called autophagy, which helps to protect cells by degrading dysfunctional proteins and organelles. Insufficient activity of this pathway is considered to be a feature of most age-related neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and other forms of dementia. One prominent consequence of autophagy inhibition is accumulation and aggregation of a protein called sequestosome-1 or p62. Most importantly, majority of inclusions observed in neurodegenerative diseases are also positive for p62 suggesting that impaired autophagy may contribute to the formation of different types of inclusions. Accumulating p62 has detrimental effect and is both a disease biomarker and a potential target for drug interventions.

The current laboratory-based studies suggest novel mechanisms regulating aggregation of p62 and this project tests if these processes have relevance to human pathology and whether they represent potential therapeutic targets.

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