Neurodegenerative disorders are common and devastating. Rationally, the most effective treatments will target pathogenetic mechanisms. While alternative - proaches, based on alleviating the symptoms of patients with Alzheimer disease, Parkinson disease, Huntington disease, prion disorders or amyotrophic lateral sc- rosis, can be expected to reduce suffering, studies of pathogenesis of these a- related disorders will be most important for enabling early diagnosis and the creation of preventative and curative treatments. It is in this context that a recent IPSEN rd meeting (The 23 Colloque Medecine ´ et Recherche, April 28, 2008) focused on a role for disruption of intracellular traf?cking in neurodegenerative disorders. The meeting captured emerging insights into pathogenesis from disrupted traf?cking and processing of proteins implicated in age-related degeneration. Protein folding, traf?cking and signaling were the principal topics covered at the meeting. Importantly, the presenters pointed to the importantly intersection of these themes. While the proteolytic processing of APP into its toxic product, the A? peptide, is an intensive focus of work in many laboratories, it is only relatively recently that investigators have begun to examine in depth the cellular compartments and traf?cking events that mediate APP processing and how derangement of tr- ?cking pathways could impact them.
This book explores the role of sub-cellular trafficking in the pathogenesis, treatment and prevention of neurodegenerative diseases. Recent findings point to faulty trafficking as contributing to the dysfunction and degeneration of neurons and neural circuits. Increasingly, research is targeting the mechanisms responsible and means to address them therapeutically. Many adult onset neurodegenerative diseases appear to arise from the accumulation of misfolded, neurotoxic peptides. This book investigates the ways in which sub-cellular trafficking pathways play a role both in the pathological accumulation of these misfolded proteins and in attempts to clear them. Because subcellular protein trafficking has an important role in the biology of neuronal function and survival, this also addresses how trophic factors maintain cell: cell interactions and how the underlying mechanisms may be compromised in neurodegenerative diseases. Examples where the use of such trophic factors may provide a way to modify neurodegenerative diseases are investigated.