Axonal transport defects in neurodegenerative diseases.
Adult-onset neurodegenerative diseases (AONDs) comprise a heterogeneous group of neurological disorders characterized by a progressive, age-dependent decline in neuronal function and loss of selected neuronal populations. Alterations in synaptic function and axonal connectivity represent early and critical pathogenic events in AONDs, but molecular mechanisms underlying these defects remain elusive. The large size and complex subcellular architecture of neurons render them uniquely vulnerable to alterations in axonal transport (AT). Accordingly, deficits in AT have been documented in most AONDs, suggesting a common defect acquired through different pathogenic pathways. These observations suggest that many AONDs can be categorized as dysferopathies, diseases in which alterations in AT represent a critical component in pathogenesis. Topics here address various molecular mechanisms underlying alterations in AT in several AONDs. Illumination of such mechanisms provides a framework for the development of novel therapeutic strategies aimed to prevent axonal and synaptic dysfunction in several major AONDs.
Morfini
Gerardo A
GA
Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, Illinois 60612, USA. gmorfini@uic.edu
Burns
Matthew
M
Binder
Lester I
LI
Kanaan
Nicholas M
NM
LaPointe
Nichole
N
Bosco
Daryl A
DA
Brown
Robert H
RH
Brown
Hannah
H
Tiwari
Ashutosh
A
Hayward
Lawrence
L
Edgar
Julia
J
Nave
Klaus-Armin
KA
Garberrn
James
J
Atagi
Yuka
Y
Song
Yuyu
Y
Pigino
Gustavo
G
Brady
Scott T
ST
D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D008869:Microtubule-Associated Proteins; D016875:tau Proteins