Axonal transport in Neurodegenerative diseases

FALZONE T

Congreso; Pew Fellows Reunion; 2014

Pew Charitable trust

The research in my laboratory is directed to understand how high polarized cells such as neurons deal with the transport and delivery of different intracellular cargos that support normal neuronal function and to answer how transport defects may underlay the induction of neurodegenerative diseases. To unravel the complexity of the axonal transport system we put together molecular genetics, cell biology, biochemistry and live imaging techniques in primary cultured neurons, mouse models and human derived neurons to uncover the dynamics and regulation of intracellular cargos. We have recently revealed the axonal motion regimes of the proteasome degradative machinery that support the homogeneous distribution of this complex and exposed the interaction between proteasomes and lysosomes for distal protein degradation in neurons. We are now devoting our efforts to induce axonal transport defects in human stem cell derived neurons to comprehend the role of intracellular dynamics in the manifestation and progression of Alzheimer?s and Parkinson?s and to discover novel genetic interactions between the transport system and known proteins involved in disease. Understanding the intricacy of the intracellular mechanisms that drive organelles and vesicles inside neurons will provide invaluable knowledge to design and test future therapies directed to ameliorate and halt the progression of neurodegenerative diseases.