Axonal transport defects: a common theme in neurodegenerative diseases.
A core pathology central to most neurodegenerative diseases is the misfolding, fibrillization and aggregation of disease proteins to form the hallmark lesions of specific disorders. The mechanisms underlying these brain-specific neurodegenerative amyloidoses are the focus of intense investigation and defective axonal transport has been hypothesized to play a mechanistic role in several neurodegenerative disorders; however, this hypothesis has not been extensively examined. Discoveries of mutations in human genes encoding motor proteins responsible for axonal transport do provide direct evidence for the involvement of axonal transport in neurodegenerative diseases, and this evidence is supported by studies of animal models of neurodegeneration. In this review, we summarize recent findings related to axonal transport and neurodegeneration. Focusing on specific neurodegenerative diseases from a neuropathologic perspective, we highlight discoveries of human motor protein mutations in some of these diseases, as well as illustrate new insights from animal models of neurodegenerative disorders. We also review the current understanding of the biology of axonal transport including major recent findings related to slow axonal transport.
Roy
Subhojit
S
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104-4283, USA.
Zhang
Bin
B
Lee
Virginia M-Y
VM
Trojanowski
John Q
JQ
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D006801:Humans; D008868:Microtubule Proteins / Q000235:genetics; D008959:Models, Neurological; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000145:classification / Q000235:genetics / Q000503:physiopathology*
D008868:Microtubule Proteins