title: Novel molecular biomarkers at the blood-brain barrier in ALS.
abstract: Recently neuroinflammation has gained a particular focus as a key mechanism of ALS. Several studies in vivo as well as in vitro have nominated immunoglobulin G (IgG) isolated from ALS patients as an active contributor to disease onset and progression. We have shown that ALS IgG affects astroglial Ca(2+) excitability and induces downstream activation of phosphatidylinositol 3-kinase. These studies were hampered by a lack of knowledge of the pathway of entry of immune factors in the CNS. Our MRI data revealed the blood-brain barrier BBB leakage and T cell infiltration into brain parenchyma in ALS G93A rats. Since astrocyte ensheathes blood vessel wall contributing to BBB stability and plays an important role in ALS pathogenesis, we have studied astrocytic membrane proteins water channel aquaporin-4 and the inwardly rectifying potassium channel. In this review, we will summarize data related to BBB disruption with particular emphasis on impaired function of astrocytes in ALS. We will discuss implication of membrane proteins expressed on astrocytic endfeet, aquaporin-4, and inwardly rectifying potassium channel in the pathology of ALS. In addition to ALS-specific IgGs, these membrane proteins are proposed as novel biomarkers of the disease.
authors.affiliation: Center for Laser Microscopy, Institute for Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski Trg 16, POB 52, 11000 Belgrade, Serbia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Bataveljic
authors.affiliation: Center for Laser Microscopy, Institute for Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski Trg 16, POB 52, 11000 Belgrade, Serbia.
authors.forename: Milena
authors.initials: M
authors.lastname: Milosevic
authors.affiliation: Center for Laser Microscopy, Institute for Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski Trg 16, POB 52, 11000 Belgrade, Serbia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Radenovic
authors.affiliation: Center for Laser Microscopy, Institute for Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski Trg 16, POB 52, 11000 Belgrade, Serbia.
authors.forename: Pavle
authors.initials: P
authors.lastname: Andjus
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000473:pathology; D000818:Animals; D051401:Aquaporin 4 / Q000097:blood; D001253:Astrocytes / Q000378:metabolism; D015415:Biomarkers / Q000097:blood*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D051381:Rats
chemical_list: D051401:Aquaporin 4; D015415:Biomarkers; D007074:Immunoglobulin G