Astrocytes in the damaged brain: molecular and cellular insights into their reactive response and healing potential
Résumé
Long considered merely a trophic and mechanical support to neurons, astrocytes have progressively taken the center stage as their ability to react to acute and chronic neurodegenerative situations became increasingly clear. Reactive astrogliosis starts when trigger molecules produced at the injury site drive astrocytes to leave their quiescent state and become activated. Distinctive morphological and biochemical features characterize this process (cell hypertrophy, upregulation of intermediate filaments, and increased cell proliferation). Moreover, reactive astrocytes migrate towards the injured area to constitute the glial scar, and release factors mediating the tissue inflammatory response and remodeling after lesion. A novel view of astrogliosis derives from the finding that subsets of reactive astrocytes can recapitulate stem cell/progenitor features after damage, fostering the concept of astroglia as a promising target for reparative therapies. But which biochemical/signaling pathways modulate astrogliosis with respect to both the time after injury and the type of damage? Are reactive astrocytes overall beneficial or detrimental for neuroprotection and tissue regeneration? This debate has been animating this research field for several years now, and an integrated view on the results obtained and the possible future perspectives is needed. With this Commentary article we have attempted to answer the above-mentioned questions by reviewing the current knowledge on the molecular mechanisms controlling and sustaining the reaction of astroglia to injury and its stem cell-like properties. Moreover, the cellular/molecular mechanisms supporting the detrimental or beneficial features of astrogliosis have been scrutinized to gain insights on possible pharmacological approaches to enhance astrocyte neuroprotective activities.
Mots clés
Ado
AMPA
AP1
AQP
BBB
BDNF
bFGF
bHLH
BMP
CNS
CNTF
COX-2
CREB
CSPGs
ERK
EGF
Eph4A
Epo
ET1
ET-R
GABA
GDNF
GF
GFAP
GLAST
GLT1
GS
IFNβ
IFNγ
IGF1
IL1β
IL2
IL6
IL10
JAK
Lcn2
MAPK
MMP
mTOR
NFAT
NFkB
NGF
NT3
p38MAPK
PTEN
SOCS
SOD
STAT
TGFα
TGFβ
TNFα
VCAM1
VEGF
extracellular nucleotides
cytokines
glial scar
neural stem cells
reactive astrogliosis
brain repair.
brain repair
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