Este jueves, 23/09 a las 14 hs, el Dr.Gerardo Morfini presentará en nuestro auditorio virtual:
Squid giant axons provide clues on mechanisms linking protein misfolding, alterations in kinase signaling, and axonal pathology in human neurodegenerative diseases


Axonal transport (AT), a complex set of microtubule-dependent intracellular trafficking events powered by motor proteins, allows the delivery of membrane-bounded organelles to discrete subcellular compartments. Owing the complex cellular architecture of neurons, AT is crucial for the sustained maintenance of pre- and post-synaptic compartments sustaining neuronal connectivity and survival. In support, mutations affecting functionality of microtubule-based motors (e.g; conventional kinesin and cytoplasmic dynein) responsible for the execution of AT promote synaptic dysfunction and axonal degeneration. Relevant to human health, neurons affected in a wide variety of unrelated neurodegenerative conditions feature AT deficits, synaptic alterations, and axonal pathology early in the course of disease, but mechanisms underlying these signature pathogenic events remain elusive. An understanding of such mechanisms could facilitate the development of therapeutic strategies aimed to preserve neuronal connectivity in these diseases.
Over the last decade, studies using the isolated squid axoplasm preparation by our group revealed unique toxic effects of various unrelated neuropathogenic mutant proteins on AT, which were mediated by selected protein kinases. Notably, abnormal patterns of protein phosphorylation represent early pathological features of neurons affected in most human neurodegenerative diseases. These observations suggest that the axonal degeneration phenotype characteristic of affected neurons might result, at least in part, from aberrant activation of protein kinases involved in the regulation of AT and other cellular processes sustaining neuronal function. In this talk, I will present findings from our work on tauopathies and motor neuron diseases providing support to this notion. Collectively, these findings suggests a scenario were disease-related proteins alter homeostatic maintenance of kinase signaling through different mechanisms involving a common theme: misfolding and aberrant exposure of biologically active domains.
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