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FORESSI, Nahuel Naum

SECyT-doctoral fellow at UNC
Director: M. Soledad Celej

PhD Thesis Topic

Molecular studies of pathogenic species of Tau and their role in neurodegenerative disorders
The pathological hallmark of neurodegenerative diseases, such as Alzheimer’s disease (AD), frontotemporal lobar degeneration (FTD), Lewy body disease (Larbd), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (WHEN) is the presence of protein aggregates. In many of these diseases, protein aggregates spread through the brain following characteristic patterns. Although each of these neurodegenerative disorders exhibits accumulation of a specific protein or peptide, there is considerable clinical and pathological overlap among them.
The amyloid deposition of hyperphosphorylated Tau is the hallmark of AD and several dementias. However, co-deposition with the Parkinson’s related protein α-synuclein (AS) is observed in many cases. Understanding the role of these proteins in these disorders as well as their cross-talk requires the elucidation of the structural bases of amyloidogenesis and neurotoxicity. In this context, the main aim of this project is to identify the molecular determinants of pathogenic species of Tau that modulate its aggregation, toxicity and interaction with AS, contributing to the understanding of the etiology and spreading of the diseases.