title: Mitochondrial traffic jams in Alzheimer's disease - pinpointing the roadblocks.
abstract: The vigorous axonal transport of mitochondria, which serves to distribute these organelles in a dynamic and non-uniform fashion, is crucial to fulfill neuronal energetic requirements allowing the maintenance of neurons structure and function. Particularly, axonal transport of mitochondria and their spatial distribution among the synapses are directly correlated with synaptic activity and integrity. Despite the basis of Alzheimer's disease (AD) remains enigmatic, axonal pathology and synaptic dysfunction occur prior the occurrence of amyloid-β (Aβ) deposition and tau aggregation, the two classical hallmarks of this devastating neurodegenerative disease. Importantly, the early stages of AD are marked by defects on axonal transport of mitochondria as denoted by the abnormal accumulation of mitochondria within large swellings along dystrophic and degenerating neuritis. Within this scenario, this review is devoted to identify the molecular "roadblocks" underlying the abnormal axonal transport of mitochondria and consequent synaptic "starvation" and neuronal degeneration in AD. Understanding the molecular nature of defective mitochondrial transport may provide a new avenue to counteract AD pathology.
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
authors.forename: Sónia C
authors.initials: SC
authors.lastname: Correia
authors.affiliation: Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Laboratory of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. Electronic address: venta@ci.uc.pt.
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D001693:Biological Transport, Active; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009443:Neuritis / Q000378:metabolism* / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer's disease; Amyloid-β; Mitochondrial bioenergetics; Mitochondrial dynamics; Mitochondrial transport; Synapse; Tau