Abstract
This short review analyses the possible molecular events linking a general program of death such as apoptosis to highly specific intracellular pathways involving the function and degradation of two proteins tau and amyloid precursor protein which in their aggregated state constitute the hallmark of Alzheimer disease. By surveying the recent studies carried out in ‘in vitro’ neuronal cultures with special emphasis to cerebellar granule neurons the apparent correlation between onset of apoptosis, tau cleavage with formation of potential toxic fragments, and activation of an amyloidogenic route are discussed. Within this framework, proteasomes seem to play a crucial role upstream of the proteolytic cascade involving calpain(s) and caspase(s) by contributing to tau and amyloid precursor protein-altered breakdown and consequent tendency to aggregation of their degradation fragments. Thus, apoptotic death due to altered supply of anti apoptotic agents, neurotrophic factors, deafferentiation or other causes, may constitute a major trigger of the onset of Alzheimer disease.
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Canu, N., Calissano, P. In vitro cultured neurons for molecular studies correlating apoptosis with events related to Alzheimer disease. Cerebellum 2, 270–278 (2003). https://doi.org/10.1080/14734220310004289
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DOI: https://doi.org/10.1080/14734220310004289