title: Amyotrophic lateral sclerosis: a neurovascular disease.
abstract: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease with a complicated pathogenesis. Compelling evidence indicates impairment of all neurovascular unit components including the blood-brain and blood-spinal cord barriers (BBB/BSCB) in both patients and animal models, leading to classification of ALS as a neurovascular disease. The present review provides an updated analysis of the normal and impaired BBB/BSCB, focusing on the ALS-altered barrier. Here we describe the roles of cellular components, tight junctions, transport systems, cell interactions, cytokines, matrix metalloproteinases, and free radicals in the BBB/BSCB disruption, along with recent evidence from experimental and clinical ALS studies. The BBB/BSCB is a promising research area in ALS and this review will reveal some aspects of microvascular pathology in ALS and hopefully provide ideas for the development of new therapeutic strategies.
authors.affiliation: Center of Excellence for Aging and Brain Repair, University of South Florida, College of Medicine, Tampa, FL 33612, USA. sgarbuzo@health.usf.edu
authors.forename: Svitlana
authors.initials: S
authors.lastname: Garbuzova-Davis
authors.forename: Maria C O
authors.initials: MC
authors.lastname: Rodrigues
authors.forename: Diana G
authors.initials: DG
authors.lastname: Hernandez-Ontiveros
authors.forename: Michael K
authors.initials: MK
authors.lastname: Louis
authors.forename: Alison E
authors.initials: AE
authors.lastname: Willing
authors.forename: Cesario V
authors.initials: CV
authors.lastname: Borlongan
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002490:Central Nervous System / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000378:metabolism / Q000503:physiopathology; D006801:Humans