Neurobiology

In Trieste the Molecular Pathology Group (Buratti) investigates aberrant pre-mRNA processing defects that lead to neurodegeneration. In particular, it studies the biological properties of TDP43, a nuclear factor involved in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD).

Highlights 

In recent years, Emanuele Buratti’s Group delivered influential advances on TDP-43 biology across ALS/FTD and related disorders. The lab has helped define phosphorylation-specific “strain” signatures of pathological TDP-43 using a pS369 antibody in human brain tissue, bolstering the idea of conformational diversity in TDP-43 proteinopathies.  In parallel, it has reported a study showing that the cellular milieu (neuronal vs muscle) powerfully reshapes TDP-43’s RNA-processing functions linking cell-type–specific splicing programs to pathology in both the nervous system and myopathies. The lab has been part of a multi-center Nature paper revealing how loss of nuclear TDP-43 – together with common ALS-risk SNPs -drives mis-splicing and depletion of UNC13A, providing a concrete genetic–molecular route from TDP-43 dysfunction to synaptic failure in ALS.  The Group has broadened the landscape with a peer-reviewed overview connecting TDP-43 to viral infections (e.g., HIV, enteroviruses, SARS-CoV-2), outlining mechanistic overlaps between infection-triggered pathways and neurodegeneration.  Recently published works showing that TDP-43 and the disease-modifier RGNEF can antagonistically control axon-guidance genes via long-intron processing, underscoring how combinatorial RBP loss-of-function can shape neuronal vulnerability in disease.