Connexins as therapeutic targets in neurological and neuropsychiatric disorders

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1867

Article

Charveriat, M.¹  Mouthon, F.¹  Rein, W.¹  Verkhratsky, A.^2,3 

[1] Theranexus, 60 Ave Rockefeller, F-69008 Lyon, France

[2] Univ Manchester, Fac Biol Med & Hlth, Manchester M13 9PT, Lancs, England

[3] IKERBASQUE, Achucarro Ctr Neurosci, Basque Fdn Sci, Bilbao 48011, Spain

关键词: Astrocyte;    Gap junctions;    Connexins;    Hemichannels;    CNS drugs;    Neuropsychiatric diseases;    Neurodegenerative diseases;    Connexin-modulating drugs;   

DOI  :  10.1016/j.bbadis.2021.166098

来源: Elsevier

【 摘 要 】

Astrocytes represent the reticular part of the central nervous system; gap junctions formed by connexins Cx43, Cx30- and Cx26 provide for homocellular astrocyte-astrocyte coupling, whereas connexins Cx30, Cx32, Cx43, and Cx47 connect astrocytes and oligodendrocytes. Astroglial networks are anatomically and functionally segregated being homologous to neuronal ensembles. Connexons, gap junctions and hemichannels (unpaired connexons) are affected in various neuropathologies from neuropsychiatric to neurodegenerative diseases. Manipulation of astrocytic connexins modulates the size and outreach of astroglial syncytia thus affecting astroglial homeostatic support. Modulation of astrocytic connexin significantly modifies pharmacological profile of many CNS drugs, which represents an innovative therapeutic approach for CNS disorders; this approach is now actively tested in pre-clinical and clinical studies. Wide combination of connexin modulators with CNS drugs open new promising perspectives for fundamental studies and therapeutic strategies.

【 授权许可】

Free