Elusive roles for reactive astrocytes in neurodegenerative diseases.
Astrocytes play crucial roles in the brain and are involved in the neuroinflammatory response. They become reactive in response to virtually all pathological situations in the brain such as axotomy, ischemia, infection, and neurodegenerative diseases (ND). Astrocyte reactivity was originally characterized by morphological changes (hypertrophy, remodeling of processes) and the overexpression of the intermediate filament glial fibrillary acidic protein (GFAP). However, it is unclear how the normal supportive functions of astrocytes are altered by their reactive state. In ND, in which neuronal dysfunction and astrocyte reactivity take place over several years or decades, the issue is even more complex and highly debated, with several conflicting reports published recently. In this review, we discuss studies addressing the contribution of reactive astrocytes to ND. We describe the molecular triggers leading to astrocyte reactivity during ND, examine how some key astrocyte functions may be enhanced or altered during the disease process, and discuss how astrocyte reactivity may globally affect ND progression. Finally we will consider the anticipated developments in this important field. With this review, we aim to show that the detailed study of reactive astrocytes may open new perspectives for ND.
Commissariat à l'Energie Atomique et aux Energies Alternatives, Département des Sciences du Vivant, Institut d'Imagerie Biomédicale, MIRCen Fontenay-aux-Roses, France ; Neurodegenerative Diseases Laboratory, Centre National de la Recherche Scientifique, Université Paris-Sud, UMR 9199 Fontenay-aux-Roses, France.
Lucile
L
Ben Haim
Commissariat à l'Energie Atomique et aux Energies Alternatives, Département des Sciences du Vivant, Institut d'Imagerie Biomédicale, MIRCen Fontenay-aux-Roses, France ; Neurodegenerative Diseases Laboratory, Centre National de la Recherche Scientifique, Université Paris-Sud, UMR 9199 Fontenay-aux-Roses, France.
Maria-Angeles
MA
Carrillo-de Sauvage
Commissariat à l'Energie Atomique et aux Energies Alternatives, Département des Sciences du Vivant, Institut d'Imagerie Biomédicale, MIRCen Fontenay-aux-Roses, France ; Neurodegenerative Diseases Laboratory, Centre National de la Recherche Scientifique, Université Paris-Sud, UMR 9199 Fontenay-aux-Roses, France.
Kelly
K
Ceyzériat
Commissariat à l'Energie Atomique et aux Energies Alternatives, Département des Sciences du Vivant, Institut d'Imagerie Biomédicale, MIRCen Fontenay-aux-Roses, France ; Neurodegenerative Diseases Laboratory, Centre National de la Recherche Scientifique, Université Paris-Sud, UMR 9199 Fontenay-aux-Roses, France.
Carole
C
Escartin
Alzheimer's disease; Huntington's disease; Parkinson's disease; amyotrophic lateral sclerosis; astrocyte reactivity; neuroinflammation; neuron-astrocyte interactions